GBV and Livelihoods - Gender Based Violence

POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
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Wednesday 2 May 2012, 10.45 – 11.45
POSTER VIEWING II
MUSCLE DISORDERS
111. THE IMPACT OF FATIGUE IN PATIENTS WITH
IDIOPATHIC INFLAMMATORY MYOPATHY: A MIXED
METHOD STUDY
Richard Campbell1,2, Darija Hofmann1, Stephani Hatch3,
Patrick Gordon1,2 and Heidi Lempp1
1
Academic Rheumatology, King’s College, London, United Kingdom;
2
Rheumatology, King’s College Hospital NHS Foundation Trust,
London, United Kingdom; 3Psychological Medicine, Institute of
Psychiatry, King’s College, London, United Kingdom
112. IMMUNOHISTOCHEMICAL MAJOR
HISTOCOMPATIBILITY COMPLEX CLASS I AND II
EXPRESSION IN IDIOPATHIC INFLAMMATORY MYOPATHIES
Leena Das1, Peter Blumbergs2 and Vidya Limaye1
1
Rheumatology, Royal Adelaide Hospital, Adelaide, South Australia,
Australia; 2Hanson Institute, Centre for Neurological Diseases,
University of Adelaide, Adelaide, South Australia, Australia
Background: Idiopathic inflammatory myopathies (IIM) are a group of
heterogeneous autoimmune disorders including polymyositis (PM),
dermatomyositis (DM) and sporadic inclusion body myositis (IBM).
There is no concensus as to the minimal histological criteria required
for the diagnosis of IBM and in the absence of "rimmed vacuoles" the
distinction from PM may be difficult. Major histocompatibility complex
(MHC) class I and II antigens are not detectable in normal muscle and
it has been suggested that MHC class I expression may be useful in
the diagnosis of IIM. The aim was to study the pattern of MHC class I
and II expression in different subgroups of IIM.
113. EVIDENCE FOR IMMUNOTHERAPY IN
DERMATOMYOSITIS AND POLYMYOSITIS:
A SYSTEMATIC REVIEW
Erin Vermaak1 and Neil McHugh1
1
Department of Rheumatology, Royal National Hospital for
Rheumatic Diseases, Bath, United Kingdom
Background: Dermatomyositis (DM) and polymyositis (PM) are rare
chronic inflammatory disorders of muscle. The morbidity and mortality
associated with these conditions remains significant despite treatment, which typically begins with high-dose corticosteroids. Secondline interventions such as immunosuppressants, immunomodulators
and biologics are commonly used in clinical practice, however there
are no clear evidence-based guidelines directing their use. We
systematically assessed the evidence for immunotherapy in DM and
PM.
Methods: Relevant studies were identified through Ovid Medline and
PubMed database searches. Bibliographies of relevant studies were
scrutinized for other potentially relevant citations, and research
registers of ongoing trials and international conference proceedings
were examined to identify research in progress or data as yet
unpublished. Randomized controlled trials and experimental studies
without true randomization (quasi-randomized) including adult patients
with definite or probable DM or PM were evaluated. Trials involving
patients with possible, early or mild disease were excluded, as were
those where diagnostic certainty was unknown or diagnostic criteria
had not been specified. Any type of immunotherapy was considered.
Improvement in muscle strength was the primary outcome. Secondary
outcomes included improvements in patient and physician global
scores, physical function and muscle enzymes. Studies not assessing
these outcomes were excluded. Using predetermined criteria, the two
authors independently selected trials for inclusion and then assessed
these for quality.
Results: 1246 citations were retrieved. 11 trials were identified as
potentially relevant, 3 were excluded after full text review. One further
trial was identified after hand-searching reference lists. 9 studies were
included for full analysis. Differences in trial design and quality, and
variable reporting of baseline characteristics and outcomes made
direct comparison impossible. Although no one treatment can be
recommended on the basis of this review, improved outcomes were
demonstrated with a number of agents including methotrexate,
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Background: Fatigue is a core symptom of idiopathic inflammatory
myopathies (IIM) and impacts on quality of life more than any other
common symptom according to findings from our past research
project. Due to the subjective nature of fatigue and the lack of
evidence-based therapies currently available, the symptom is often
overlooked. Generic questionnaires such as FACIT-F show good
reliability and validity, however, disease-specific tools are not currently
available. The purpose of this study is to explore the symptoms of
fatigue with patients beyond the confines of generic questionnaires.
Methods: A purposive sample of 14 patients (stratified by gender,
ethnicity, age, disease duration) with IIM were recruited from a tertiary
outpatient clinic and invited to an interview study in person or via
telephone, including the completion of two fatigue questionnaires
(Facit-F and Fatigue Severity Scales). Patients invited to take part had
already been identified as experiencing fatigue in a previous study.
Content analysis of the transcribed interviews and single counting
were applied to identify themes.
Results: Transcripts from interviews were available from 12 patients
(8 female; mean age 55.5 (SD 12.68) with mean disease duration of 5.3
(SD 4.0) years). 6 were retired, 5 in full time employment and 1 in part
time employment. Mean FACIT-F for the group was 24.6 (SD 13.3) and
fatigue severity scale 4.7 (SD 1.5). The following six themes emerged:
1) Fatigue characteristics (e.g. lack of refreshment with rest or sleep,
fluctuation of severity and predictability; 2) Exacerbating factors (e.g.
low mood, sleep disturbance); 3) Impact on life (e.g. compromised
work productivity, social and family commitments; 4) Coping strategies (e.g. pacing, planning ahead; 5) Communication with clinic staff
re. fatigue (e.g. perceived lack of sympathy, availability of effective
treatment); 6) Communication with family/friends (e.g. underplaying
symptoms, seeking support).
Conclusions: The results show that IIM fatigue, (as in other
autoimmune conditions such as rheumatoid arthritis) is different from
tiredness. It is intrusive and affects patients’ public and private roles,
contributions and responsibilities. Fatigue has been shown to
associate with low mood in IIM. The causal link between these
issues needs to be explored further. The results provide a platform for
the future development of an IIM disease-specific fatigue scale
Disclosure statement: All authors have declared no conflicts of
interest.
Methods: Retrospective study performed on 120 muscle biopsies
including 61 PM, 14 DM and 45 IBM during the period of January 2003
to October 2011. Cryostat sections of skeletal muscle (mainly
quadriceps) were immunostained with antibodies against MHC class
I and II antigens (human leukocyte antigen(HLA)-DP,DQ,DR antigens,
clone CR3/43 and HLA -ABC antigen, clone W6/32, respectively) using
standard protocols. The sarcolemmal and sarcoplasmic staining was
graded on a scale of 0 to 5þ by two independent observors. 0: no
staining, 1þ: up to 10% fibres, 2þ: 10-25%, 3þ: 25-50%, 4þ: 50-99%
and 5þ 100%.
Results: In PM variable MHC class I expression was present in all
61 cases (> or ¼ 3þ in 48 and ¼ or <2þ in 13 biopsies). MHC class 2
expression was absent in 8 biopsies and variably positive in the
remainder (¼ or >3þ in 24 and ¼ or < 2þ in 29).In DM variable MHC
class I expression in all 14 cases (> or ¼ 3þ in 12 and ¼ or < 2þ in 2).
MHC class II expression was present in 13/14 cases (> or ¼ 3þ in 4
and ¼ or < 2þ in 9). All the muscle biopsies showed a characteristic
perifascicular pattern of staining with both antibodies and increased
intensity of staining of both the vasculature and muscle fibres with
MHC class II. In IBM all 45 cases showed ¼ or >3þ MHC 1 expression
and 35 biopsies showed ¼ or >3þ MHC 2 staining.
Conclusions: In DM there was 100% MHC class I expression and a
characteristic perifascicular pattern of staining (MHC class I and II). In
PM variable MHC class I expression was present in all cases and
8 biopsies showed negative MHC II class staining. In IBM MHC class I
and II expression was less variable than in PM with all biopsies
showing strong MHC I class immunoreactivity (5þ in 30). Evaluation of
MHC class I and II immunostaining is helpful in the diagnosis of
autoimmune myopathies and in differentiating IIM subsets.
Disclosure statement: All authors have declared no conflicts of
interest.
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Wednesday 2 May 2012, 10.45 – 11.45
POSTER VIEWING II
TABLE 1 Summary of included trials
Study
Intervention
Conclusion
Bunch et al. 1980
Hollingworth et al. 1982
Miller et al. 1992
Dalakas et al. 1993
Villalba et al. 1998
Vencovsky et al. 2000
van de Vlekkert et al. 2010
The Muscle Study Group 2011
Miyasaka et al. 2011
Pred þ AZA vs Pred þ placebo
ALG þ AZA þ Pred vs Pred
PEX vs Leukapheresis vs Sham apheresis
IVIg vs Placebo
Pred þ MTX þ AZA vs Pred þ IV MTX
Pred þ CsA vs Pred þ MTX
Pred vs Dex
Pred þ ETAN vs Pred þ placebo
IVIg vs Placebo
No additional benefit with AZA at 3 months
NS trend toward benefit with ALG þ AZA
PEX/leukapheresis of no benefit
IVIg beneficial in refractory DM
NS trend toward benefit with MTX þ AZA
MTX and CsA equally efficacious, but MTX better tolerated, less toxic, and cheaper
Dex not superior to pred, but fewer side effects observed
No additional benefit with ETAN, but steroid-sparing effect observed
IVIg of no benefit
ALG, anti-lymphocyte globulin; AZA, azathioprine; CsA, ciclosporin; Dex, dexamethasone; ETAN, etanercept; IV, intravenous; IVIg, intravenous immunoglobulin; MTX,
methotrexate; NS, non-significant; PEX, plasma exchange; Pred, prednisolone.
azathioprine,
ciclosporin
and
intravenous
immunoglobulin.
Plasmapheresis and leukapheresis were of no benefit.
Conclusions: More high quality randomized controlled trials are
needed to establish the role of second-line agents in the treatment of
DM and PM.
Disclosure statement: All authors have declared no conflicts of
interest.
Mark H. Edwards1, Karen Jameson1, Avan Aihie Sayer1,
Elaine Dennison1 and Cyrus Cooper1
1
MRC Lifecourse Epidemiology Unit, University of Southampton,
Southampton, United Kingdom
Background: Sarcopenia is common in later life and is associated
with subsequent disability. However, the definition of sarcopenia is
often problematic; for this reason the European Working Group on
Sarcopenia in Older People has recently proposed a practical clinical
definition for age-related sarcopenia which requires the presence
of both low muscle mass and low muscle function (strength or
performance). The extent to which these different components of
sarcopenia correlate with bone structure, bone mineral content, risk of
falls, and ultimately fracture, remains uncertain. We address these
issues in a large prospective population-based cohort study of
musculoskeletal ageing.
Methods: We studied 1579 men and 1418 women at a baseline clinic
that included completion of a health questionnaire and detailed
anthropometric data. Grip strength was measured using a Jamar
hand-held dynamometer and gait speed was assessed by a 3 metre
walk test. Subsequently 1168 men and 1131 women completed a
postal questionnaire detailing fall and fracture history a mean of
5.5 years later (range 2.9-8.8yrs). A subset of 313 men and 318
women, returned for a follow-up clinic a mean of 4.4 years after the
baseline clinic (range 2.6-6.2 yrs) at which grip and gait speed were reassessed and peripheral quantitative computed tomography (pQCT)
examination of the calf and forearm was performed using a Stratec
4500 instrument to assess muscle cross-sectional area and bone
parameters.
Results: The mean participant age (SD) at baseline was 66.2
(2.8) years. After adjustment for age, height and weight, a higher
forearm and calf muscle area were both associated with higher bone
strength (strength strain index and fracture load) and bone area in the
corresponding limb (p < 0.001 for forearm; p < 0.05 for calf).
Relationships between muscle area and bone density were inconsistent, and only statistically significant between forearm muscle area
and radial total and trabecular density at the 4% site in women
(p < 0.05). While grip strength did not consistently predict bone area,
density or strength in either sex, it did predict both a lower risk of falls
reported in the previous year and incident fracture (men OR 0.93 95%
CI 0.89, 0.97 p ¼ 0.002; women OR 0.96 95% CI 0.93, 0.998 p ¼ 0.04,
for every 1 kg increase in grip strength) after adjustment for age, height
and weight.
Conclusions: Muscle area correlates strongly with bone mass, area
and strength; however, unlike muscle strength, it is not a predictor of
falls or fracture.
Disclosure statement: All authors have declared no conflicts of
interest.
115. MUSCLE OUTCOME IN PATIENTS WITH IDIOPATHIC
INFLAMMATORY MYOPATHIES
Fernando B. Salvador1,2, Carolina Huertas2,3 and David Isenberg2
1
Internal Medicine, Centro Hospitalar de Tra´s-os-Montes e Alto
Douro, Vila Real, Portugal; 2Rheumatology, University College
Background: Idiopathic inflammatory myopathies (IIM) are systemic
autoimmune diseases characterized by chronic muscle inflammation
resulting in progressive usually proximal muscle weakness.
Progression is extremely variable and requires complex and different
therapeutic approaches. We reviewed the outcome of patients
(>16 years of age) presenting with IIM, notably polymyositis and
dermatomyositis (inclusion body myositis was excluded), to the
Rheumatology Department at University College London Hospital
since 1980.
Methods: From a case notes review of those patients, followed for a
minimum of three years, who fulfilled the Bohan and Peter classification criteria, we designated and characterized three muscle outcomes:
a) monophasic - patients who met all of the following: proximal muscle
strength grade 4 (medical research council scale); prednisolone (or
equivalent) reduced to 5mg/day; off immunosuppressive drugs;
normal serum levels of creatine kinase (CK). b) relapsing/remitting clear evidence of improvement with at least two of the four criteria
having been met followed by one or more exacerbation. c) chronicpersistent - not included in a) and b). In addition we noted the number
of patients who died and the causes.
Results: From the 79 patients observed (age 56 13 yrs, 72% female)
52% had monophasic outcome, 21% relapsing/remitting and 27%
chronic persistent. Patients with monophasic outcome had a mean
age at diagnosis of 43 15yrs and 71% were female. Their mean initial
CK level was 4432UI/L and antinuclear autoantibodies (ANA) were
positive in 80% and antisynthetase autoantibodies in 22%. Seven
patients (17%) died after diagnosis. Patients with relapsing/remitting
outcome had 37 13 yrs at diagnosis and all of them were female. The
initial CK level was 3862UI/L, ANA was positive in 59% and anti-Mi-2
autoantibodies were found in 18%. Three patients (18%) died after
diagnosis. Patients with chronic-persistent outcome had 37 11 yrs at
diagnosis and 52% were female. Initial CK level was 5564UI/L and
ANA was positive in less than half (48%). Five patients (24%) died after
diagnosis.
Conclusions: The majority of patients in our cohort had a monophasic
disease and approximately 80% were ANA positive. Mortality was not
significantly different however between the three groups. The highest
CK levels were noted in the chronic persistent group. This classification might be useful for collaborative studies and characterization of
the outcome in patients with IIM.
Disclosure statement: All authors have declared no conflicts of
interest.
ORTHOPAEDICS AND REHABILITATION
116. A CASE–CONTROL STUDY OF RISK FACTORS FOR
ELECTIVE HIP REPLACEMENT OR RESURFACING
SURGERY IN HIV-INFECTED ADULTS
Elizabeth J. Jackson1, Annie Middleton1, Duncan Churchill2 and
Karen Walker-Bone1,2
1
Rheumatology, Brighton & Sussex Medical School, Brighton,
United Kingdom; 2HIV and GU Medicine, Brighton & Sussex
University Hospitals NHS Trust, Brighton, United Kingdom
Background: Since the introduction of combination antiretroviral
therapy (cART), life expectancy with HIV infection has increased.
However, previously unrecognized long-term complications of HIV and
its treatment are emerging. Rheumatic manifestations have been
documented, including an increased risk of avascular necrosis (AVN)
and osteoporosis. To the best of our knowledge, the prevalence of
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114. MUSCLE SIZE AND STRENGTH AS PREDICTORS OF
BONE STRUCTURE, FALLS AND FRACTURES IN THE
HERTFORDSHIRE COHORT STUDY
London Hospital, London, United Kingdom; 3Rheumatology,
Hospital General Universitario Gregorio Maran˜o´n, Madrid, Spain
POSTER VIEWING II
117. CLINICAL OUTCOMES FOLLOWING MOTOR CONTROL
REHABILITATION FOR SHOULDER IMPINGEMENT
Peter R. Worsley1, Sarah Mottram1, Martin Warner1,
Dylan Morrissey2, Stephan Gadola3, Andrew Carr4, Cyrus Cooper5
and Maria Stokes1
1
Faculty of Health Sciences, University of Southampton,
Southampton, United Kingdom; 2Centre for Sports and Exercise
Medicine, Queen Mary University of London, London, United
Kingdom; 3Faculty of Medicine, University of Southampton,
Southampton, United Kingdom; 4Oxford NIHR Musculoskeletal
Biomedical Research Unit, University of Oxford, Oxford, United
Kingdom; 5MRC Lifecourse Epidemiology Unit, Southampton
University Health Trust, Southampton, United Kingdom
Background: Shoulder impingement is the most common pathology
of all shoulder pain referrals. Impingement syndrome can cause
functional disability and reduce quality of life and may contribute to the
development of rotator cuff disease. The aim of the present study was
to examine the effects of a motor control based exercise intervention
for shoulder impingement patients.
Methods: Sixteen young adults with shoulder pain (mean age
24.6 1.6, range 18-34 years, 11 males) were recruited from the
local community. Inclusion criteria were: current shoulder pain severe
enough to limit activity for more than one week and impingement
signs. Diagnostic ultrasound imaging was used to exclude participants
with complete rotator cuff tears. Mean duration of shoulder symptoms
was 16 months (range 4-36 months).Physical screening of pain
participants was conducted in order to derive a clinical presentation
of shoulder impingement using three clinical tests; Hawkins-Kennedy,
Neer’s and Painful Arc. A 10 week motor control retraining package
was targeted at correcting movement impairments of the scapula by
re-educating muscle recruitment. There were two components to the
package: 1) Motor control exercises to correct alignment and
coordination, which involve a) controlling scapular orientation during
active arm movements; b) muscle-specific exercises for trapezius and
serratus anterior; 2) Commonly used manual therapy techniques to
reduce joint and muscle restrictions. Participants underwent three data
collection sessions; pre-intervention, immediately post-intervention
and six months post-intervention (13 participants completed post). The
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primary outcome measure of pain and function was the Shoulder Pain
and Disability Index (SPADI); other questionnaires included the
Disabilities of Arm Shoulder and Hand (DASH), Oxford Shoulder
Score (OSS), Short-Form 36 (SF-36), visual analogue scale (VAS) of
pain.
Results: The SPADI scores improved on average by 10(7) and
13(6) points at the 10 week and 6 months assessments respectively.
These changes were statistically significant (p < 0.001) and reached
the Minimal Clinically Important Difference (MCID). Pain scores on the
10-point VAS also reduced immediately after and 6 months postintervention with a mean reduction of 3.4(1.5) and 4.3(2) respectively. DASH improved by 9.2(10.3) at 10 weeks and 11.8 (6.3) at
6 months, whilst small improvements were also seen in the OSS
(4.7 4) and SF-36 physical scores (3.8 4.9). Immediately postintervention the physical tests for impingement syndrome were
negative for 15/16 participants.
Conclusions: The present findings suggest that a 10 week programme of specific motor control exercises can improve function and
pain in young adults with shoulder impingement. Improvements
persisted at 6 months but effectiveness in the longer-term needs to
be examined and compared with other exercise interventions in a
randomized controlled trial involving a wider age range of shoulder
impingement patients.
Disclosure statement: All authors have declared no conflicts of
interest.
OSTEOARTHRITIS
118. WHICH RADIOLOGICAL FEATURE IS A TRUE
PREDICTOR OF CLINICAL SEVERITY IN KNEE
OSTEOARTHRITIS?
Rajeshwar N. Srivastava1 and Divya Sanghi1
1
Orthopaedic Surgery, KG Medical College, CSM Medical University,
Lucknow, India
Background: Although discordance exists between clinical and
radiographic profiles, it remains a convention to diagnosis knee
osteoarthritis(KOA) by ACR guidelines and its severity by KL grades.
This customary approach is in continuum because nothing better
could be evolved. This study was undertaken to resolve a much
debated issue as to why clinical features do not correlate significantly
with radiological KOA. We postulated that there might be a particular
reason for wide variation in the degree to which clinical symptoms
relate radiographic KOA and vice versa. The discordance noted by
many authors may probably be due to the limitations of outcome
measures in their radiographic study. We extended the radiological
features beyond those included in KL Grades and analysed them with
clinical symptoms and scores to identify which radiological feature is a
truer representative of clinical severity in KOA.
Methods: 180 cases of primary KOA were profiled for demographic,
clinical and radiological features. All the radiographs were evaluated
for nine individual radiological features (IRF) on index knees by an
orthopedic radiologist. Clinical scores were separately correlated with
all nine IRF to look for an association.
Results: Pain & functional disability were significant with increasing
KL Grades (p ¼ 0.03, p ¼ 0.02) whereas stiffness was not. On analysis
of individual radiological features, WOMAC-pain was significant
with subchondral sclerosis (p ¼ 0.04) joint space width (p ¼ 0.02),
tibiofemoral alignment (p ¼ 0.02). VAS-pain was significant with later
two and articular incongruity (p ¼ 0.00). Functional disability was
associated with medial joint space narrowing (p ¼ 0.02), tibiofemoral
alignment (p ¼ 0.03), loose bodies (p ¼ 0.04), juxtra articular osteopenia (p ¼ 0.01). However in linear regression model pain and stiffness
was significantly associated with articular incongruity (p ¼ 0.00,
p ¼ 0.01) & functional disability (p ¼ 0.04) and severity(p ¼ 0.03) with
juxtaarticular osteopenia.
Conclusions: Articular incongruity emerged a truer representative of
pain and stiffness whereas Juxtra articular osteopenia strongly
correlated with physical disability and clinical severity. This study
has essentially analysed many more of the radiological features than in
many previous studies and this may have contributed to the increased
association between clinical and radiographic features.
Disclosure statement: All authors have declared no conflicts of
interest.
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osteoarthritis (OA) in HIV infection has not been studied. In the UK,
most elective hip surgery is carried out for OA or AVN. The aim of this
study was to identify risk factors for undergoing elective hip
resurfacing or total hip replacement (THR) among HIV-infected adults.
Methods: From a cohort of 1800 patients with HIV, cases were
identified who were awaiting, or had undergone, elective hip surgery.
The clinical diagnosis prior to surgery was identified by review of plain
X-ray (and MRI scans where available). Five controls were selected for
each case, defined as HIV-infected individuals matched by age, sex
and ethnicity who had not undergone, or were not planning to
undergo, hip surgery. Data were collected from the HIV database and
clinic notes. The prevalence of known risk factors for both OA and AVN
were compared among cases and controls.
Results: The cohort of HIV-infected patients in Brighton is 90% male,
mean age 42 years with a mean 6 years HIV. From this cohort, 13
cases were identified who had received, or were awaiting, elective
THR or hip resurfacing (prevalence 0.7%). Nine had a pre-operative
diagnosis of OA and 4 AVN. Median age at time of surgery was
47.7 years, and within the OA and AVN subgroups was 48.3 years and
42.8 years respectively. The single most significant risk factor for
elective hip surgery was a history of systemic steroid use (p < 0.001).
Similarly, analysis of the subset of patients ‘diagnosed’ with OA
showed the same highly significant association (p < 0.001), as did the
subset with clinical AVN (p < 0.001). Some associations were also seen
with hyperlipidaemia. No significant associations were found with
smoking, alcohol, testosterone use, chemotherapy, radiotherapy,
statin use, CD4þ cell count, viral load, duration of HIV since diagnosis
or duration of cART.
Conclusions: This is the first epidemiological study of risk factors for
elective hip surgery in HIV-infected patients. Given their age, elective
hip surgery seems common. The single most important risk factor was
exposure to systemic glucocorticoids. This is a well-known and
important risk factor for AVN but it is interesting that this risk factor is
also highly significant amongst those presenting with what is radiographically OA. The findings suggest that the likely mechanism of OA
in these young patients is also AVN. If elective hip surgery is to be
avoided in HIV patients, prevention will need to focus on avoidance of
risk factors for AVN, including systemic glucocorticoids, the effects of
which can be potentiated by some cART, notably Ritonavir.
Disclosure statement: All authors have declared no conflicts of
interest.
Wednesday 2 May 2012, 10.45 – 11.45
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Wednesday 2 May 2012, 10.45 – 11.45
119. INFLUENCE OF DIETARY NUTRIENTS IN PREVALENCE
OF OSTEOARTHRITIS OF THE KNEE
Rajeshwar N. Srivastava1 and Divya Sanghi1
1
Orthopaedic Surgery, KG Medical College, CSM Medical University,
Lucknow, India
120. A NEW NON-INVASIVE BIOMECHANICAL THERAPY
FOR KNEE OSTEOARTHRITIS IMPROVES CLINICAL
SYMPTOMS AND GAIT PATTERNS
Avi Elbaz1, Amit Mor1, Ganit Segal1, Michael Drexler2,
Doron Norman3, Eli Peled3 and Nimrod Rozen4
1
AposTherapy Research Group, Apos Medical and Sports
Technologies, Herzliya, Israel; 2Department of Orthopedic Surgery,
Sourasky Medical Center, Tel Aviv, Israel; 3Department of Orthopedic
Surgery, Rambam Medical Center, Haifa, Israel; 4Department of
Orthopedic Surgery, HaEmek Medical Center, Afula, Israel
Background: The management of knee osteoarthritis (OA) focuses on
reducing the levels of pain and disability. Recently, a novel
biomechanical device and treatment methodology (AposTherapy)
was shown to reduce knee adduction moment while simultaneously
challenging the neuromuscular control system through perturbation.
The purpose of the study was to investigate the changes in gait
patterns and clinical measurements following treatment with a novel
biomechanical device on patients with knee OA.
Methods: 745 patients with bilateral knee OA were analysed. Patients
completed a gait test, Western Ontario and McMaster Osteoarthritis
Index (WOMAC) questionnaire and SF-36 Health Survey at baseline
and after 12 weeks. The biomechanical device was individually
calibrated to each patient. Shifting the centre of pressure, through
changes in the location of the biomechanical elements causes
realignment and reduction in knee adduction moment. Furthermore
the configuration of the biomechanical element allows training under
controlled perturbation.
Results: A significant decrease was found in WOMAC pain (28.6%)
and WOMAC function (25.2%) following three months of therapy
(p < 0.001). A significant increase was found in the patients’ physical
quality of life (17.8%) and mental quality of life (11.0%) (p < 0.001). Gait
velocity, cadence step length, stance phase and single limb support
phase improved significantly following three months of therapy (7.6%,
4.0%, 3.7% and 1.6%, respectively).
Conclusions: Our results suggest an overall improvement in the gait
patterns, level of pain, function and quality of life of patients with knee
OA following three months of AposTherapy.
Disclosure statement: A.E. holds shares in AposTherapy. A.M. holds
shares in AposTherapy. G.S. is a salaried employee of AposTherapy.
All other authors have declared no conflicts of interest.
121. FOOT CENTRE OF PRESSURE MANIPULATION AND
GAIT THERAPY INFLUENCE LOWER LIMB MUSCLE
ACTIVATION IN PATIENTS WITH OSTEOARTHRITIS OF
THE KNEE
Yulia Goryachev1, Eytan M. Debbi1, Amir Haim1,2, Nimrod Rozen3
and Alon Wolf1
1
Biorobotics and Biomechanics Lab, Faculty of Mechanical
Engineering, Technion-Israel Institute of Technology, Haifa, Israel;
2
Department of Orthopedic Surgery, Sourasky Medical Center, Tel
Aviv, Israel; 3Department of Orthopedic Surgery, HaEmek Medical
Center, Afula, Israel
Background: The purpose of this study was to determine lower limb
muscle activation changes in knee osteoarthritis patients, both
immediately after COP manipulation and when COP manipulation
was combined with continuous gait therapy (AposTherapy).
Methods: Fourteen females with medial compartment knee osteoarthritis underwent EMG analyses of key muscles of the leg. In the initial
stage, trials were carried out at four COP positions. Following this, gait
therapy was initiated for three months. The barefoot EMG was
compared before and after therapy.
Results: The average EMG varied significantly with COP in at least one
phase of stance in all examined muscles of the less symptomatic leg
and in three muscles of the more symptomatic leg. After training, a
significant increase in average EMG was observed in most muscles.
Most muscles of the less symptomatic leg showed significantly
increased peak EMG. Activity duration was shorter for all muscles of
the less symptomatic leg (significant in the lateral gastrocnemius) and
three muscles of the more symptomatic leg (significant in the biceps
femoris). These results were associated with reduced pain and
increased function.
Conclusions: COP manipulation influences the muscle activation
patterns of the leg in patients with knee osteoarthritis. When combined
with a therapy program, muscle activity increases and activity duration
decreases
Disclosure statement: All authors have declared no conflicts of
interest.
122. DIFFERENCES IN GAIT BETWEEN MEDIAL AND
FRONTAL KNEE PAIN IN PATIENTS WITH OSTEOARTHRITIS
OF THE KNEE
Ronen Debi1, Amit Mor2, Ganit Segal2, Eytan M. Debbi2, Marc
S. Cohen2, Ilya Igolnikov2, Yaron Bar Ziv3, Vadim Benkovich4,
Benjamin Bernfeld5, Nimrod Rozen6 and Avi Elbaz2
1
Department of Orthopedic Surgery, Barzilay Medical Center,
Ashkelon, Israel; 2AposTherapy Research Group, Apos, Herzliya,
Israel; 3Department of Orthopedic Surgery, Assaf Harofeh Medical
Center, Zerifin, Israel; 4Department of Orthopedic Surgery, Soroka
University Medical Center, Beer Sheva, Israel; 5Department of
Orthopedic Surgery, Carmel Medical Center, Haifa, Israel;
6
Department of Orthopedic Surgery, HaEmek Medical Center, Afula,
Israel
Background: The purpose of this study was to characterize the knee
OA gait patterns of patients with frontal knee pain and patients with
medial knee pain.
Methods: 240 patients were evaluated at one therapy centre. Patients
were divided into two groups according to the location of greatest pain
in their worse knee. Patients underwent a computerized gait analysis.
Differences in gait patterns between the two knee pain locations were
also examined within each gender.
Results: Patients with medial knee OA pain showed a significantly
slower walking speed (P < 0.01), shorter step length (P < 0.01) and
lower SLS phase (P < 0.01) compared to patients with frontal knee
pain. Significant differences were also found in each gender.
Conclusions: Patients with medial knee pain show worse spatiotemporal gait parameters than patients with frontal knee pain. These
differences are witnessed mainly between the females in each group,
whereas males differ only in single limb support. These differences
may present underlying differences in the nature of medial and frontal
knee OA pain and gender differences in compensation for knee pain
Disclosure statement: All authors have declared no conflicts of
interest.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: There is growing recognition of the importance of
nutritional factors in the maintenance of bone and joint health and that
nutritional imbalance combined with endocrine abnormalities may be
involved in the pathogenesis of Osteoarthritis (OA). The present study
sought to identify Influence of dietary nutrients in prevalence of
osteoarthritis (OA) knee.
Methods: A cross sectional study. 150 Subjects were recruited
from outpatient clinic with the diagnosis of knee Osteoarthritis (KOA)
according to the criteria of American College of Rheumatology (ACR).
Controls were age sex matched healthy subjects who were free from
disease under study. OA was radiologically graded according to
Kellgren-Lawrence (KL) grades. Body Mass Index (BMI) was recorded
by standard procedure. Dietary nutrient intakes were analysed by self
administered questionnaire including three day dietary recall and food
frequency table (FFQ).
Results: An average weight and BMI was significantly higher in
subjects with OA knee in comparison to subjects without KOA. Among
all dietary factors under study riboflavin, b-carotene, vitamin C and
vitamin D was significantly lower in subjects having OA knee in
comparison to subjects without OA knee. In unadjusted logistic
regression, lower intake quartile of riboflavin, b-carotene, vitamin C
and vitamin D having higher risk of OA knee in comparison to higher
intake quartiles. However in adjusted analysis, risk of OA knee for
riboflavin was diminished and b-carotene lose some strength but
vitamin C and D having similar strength of risk of OA knee in quartile
having lower intake. As the severity of disease was only defined by
vitamin D intake.
Conclusions: The present cross sectional study revealed that lower
intake of b- carotene, vitamin C and vitamin D intake is a risk factor for
knee OA. These nutrients might be an explanatory nutrient for the
course of OA knee and might lead to disease-modifying effect
Disclosure statement: All authors have declared no conflicts of
interest.
POSTER VIEWING II
POSTER VIEWING II
123. EFFECT OF OXYGEN TENSION AND PH ON
MITOCHONDRIAL FUNCTION IN HUMAN OSTEOARTHRITIC
ARTICULAR CHONDROCYTES
John Collins1, Robert J. Moots2, Peter D. Clegg1 and Peter I. Milner1
1
Institute of Ageing and Chronic Disease, University of Liverpool,
Leahurst Campus, Neston, United Kingdom; 2Institute of Ageing and
Chronic Disease, University of Liverpool, University Hospital Aintree,
Aintree, United Kingdom
124. STUDY SHOWS THAT ENDOGENOUS RETROVIRUS
ERV-3 IS NOT IMPLICATED IN RHEUMATOID ARTHRITIS BUT
MAY PROVIDE A BIOMARKER OF OSTEOARTHRITIS
Hora D. Ejtehadi1 and Paul N. Nelson2
1
Health Sciences, Birmingham City University, Birmingham, United
Kingdom; 2Research Institute in Healthcare Sciences, University of
Wolverhampton, Wolverhampton, United Kingdom
Background: Human endogenous retroviruses have long been
recognized as a contributory factor in the pathogenesis of certain
autoimmune diseases. ERV-3 is an inherited single-copy provirus
mapped to chromosome 7. It possesses a long open reading frame in
the env gene that is capable of producing a 65 kDa protein and
provides a physiological role in the placenta and is deleteriously linked
to congenital heart block babies. The purpose of this study was to
examine whether human endogenous retrovirus ERV-3 is associated
with autoimmune rheumatic disease.
Methods: A semi-quantitative multiplex reverse transcription polymerase chain reaction (mRT-PCR) system was designed and
optimized to investigate the mRNA expression of an envelop region
of ERV-3 in rheumatoid arthritis (RA) patients. Peripheral blood
mononuclear cells (PBMC) from 20 RA patients who fulfilled ARA
criteria were used to extract cDNA. Seventeen patients with
osteoarthritis (OA) and 27 healthy individuals were used as controls
iii97
following obtaining local ethical approval. Samples were tested in a
multiplex system and optimized for the envelope region of ERV-3. The
PCR product were analysed following gel electrophoresis and DNA
sequencing confirmed 99% homology with ERV-3.
Results: On testing PBMCs from RA, OA and control samples, ERV-3
mRNA expression was exhibited in all samples. We conducted a oneway ANOVA on pixel ratio intensity of PCR product bands on agar gel
to investigate whether ERV-3 gene expression differed between
patients (healthy vs OA vs RA). The ANOVA revealed that a significant
difference between OA patients and controls did exist (p ¼ 0.014*).
Tukey post-hoc pairwise comparison also confirmed that the only
significant difference was between healthy versus OA patient groups
(1.36 versus 2.22) with a difference of 0.8549 (95% CI from 0.1603 to
1.5496). There was an elevation of ERV-3 in OA as compared to RA
groups but was not statistically significant in this study.
Conclusions: Our preliminary data suggests that ERV-3 is not
associated with RA but could provide a marker in OA. Interestingly
the lowest level of ERV-3 gene expression was higher in the OA group
as compared to healthy and rheumatoid groups but there was no
correlation between ERV-3 expression and age in OA patients. The
presence of ERV-3 in OA needs to be further evaluated in a larger
cohort of OA patients and with other suitable controls. These studies
could then assess ERV-3 as a potential biomarker of this degenerative
disease that can have a genetic predisposition. Alternatively ERV-3
expression could be rendered a possible epiphenomenon. Overall, the
availability of a simple biomarker could be useful in osteoarthritis.
Disclosure statement: All authors have declared no conflicts of
interest.
125. DYNAMIC, CONTRAST-ENHANCED MAGNETIC
RESONANCE IMAGING OF THE OSTEOARTHRITIC KNEE IN
ASSESSMENT OF RESPONSE TO INTRA-ARTICULAR
CORTICOSTEROID
Claire Wenham1,2, Sharon Balamoody1,3, Richard Hodgson1,3 and
Philip Conaghan1,2
1
NIHR Leeds Musculoskeletal Biomedical Research Unit, University
of Leeds, Leeds, United Kingdom; 2Section of Musculoskeletal
Disease, Chapel Allerton Hospital, Leeds, United Kingdom;
3
Department of Musculoskeletal Radiology, Leeds Teaching
Hospitals Trust, Leeds, United Kingdom
Background: MRI studies have demonstrated that synovitis is very
common in painful knee OA. IA steroid, presumed to act via an antisynovial action, is commonly used for treating OA DCE MRI is a
technique by which quantitative measures of contrast agent in tissue
can be assessed, indicating vascular flow and capillary permeability. It
is known that early synovial enhancement rates correlate with
histological markers of inflammation. One previous study of largely
inflammatory arthritis subjects has shown that IA steroid results in a
reduction in early enhancement rate. However there is very little DCE
MRI data in OA.
Methods: 13 people with ACR criteria OA knee who had been referred
for IA steroid injection attended for 3T MRI of the knee pre and post
intra-articular methylprednisolone injection.
MR sequences (pre-contrast 3D slab Sagittal T1 SPGR, 96 slices
TE ¼ 2.46 ms, TR ¼ 4.3 ms, Flip Angle ¼ 308, Resolution ¼ 1.6 1.3 1.3 mm) included 30 dynamic series performed at 10 second intervals
using IV gadolinium 0.1 mmol/kg, 4 ml/s.
Subtraction images were created from the pre-contrast and final
(t ¼ 250 s) dynamic post-gadolinium images and semi-automatic
segmentation of total enhancing synovium was performed. This
segmentation was overlayed on the 4D dynamic series in order to
calculate synovial volume. Rate of early enhancement (EER) over 60
seconds (SI 60-SI baseline)/(SI baseline*60) *100% (units %/s) and late
synovial static enhancement (LSSE) (at 250 s post contrast) (SI 250-SI
baseline)/(SI baseline) *100% (units %) were calculated. A measure of
total synovial enhancement was also calculated by multiplying synovial
volume by the relative static enhancement. Clinical data including
validated pain questionnaires was recorded.
Results: Participants: mean (SD) age 61.8 (10.4) years, mean (SD)
scan interval 18 (4) days, mean pain VAS 68 mm. Median (IQR)
baseline synovial volume 68033 (51440–79220) mm3 reduced post IA
steroid to 39609 (22334–70564) mm3 (not statistically significant,
Wilcoxon p ¼ 0.09). The EER and LSSE both reduced post IA steroid
(p > 0.05) (median (IQR) reduction in EER 0.2 (-0.33 to 0.56) and in
LSSE of 8 (-0.5 to 42). However the median (IQR) total synovial
enhancement (8143342 (6003028–13636150) demonstrated a significant reduction post IA steroid to 3503678 (1776066–13167350),
p ¼ 0.023.
Baseline synovial volume or total synovial enhancement did not
correlate with baseline pain or activity VAS (r ¼ 0.24, p ¼ 0.25).
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: Articular chondrocytes reside in a unique environment
that is relatively hypoxic and acidic compared to other cells (Silver,
1975). Many in vitro models study chondrocyte biology at ambient
conditions (e.g. 21% O2, pH 7.2) which may be physiologically
inappropriate. Additionally, oxygen and pH levels reduce further in joint
disease (Gibson et al, 2008). Mitochondria are crucial cellular
organelles and may be linked with osteoarthritis (Terkeltaub et al,
2002). This study investigated the effects of different oxygen tension
and pH (in the absence or presence of the pro-inflammatory cytokine,
IL-1b), on mitochondrial membrane potential, reactive oxygen species
(ROS) levels and the glutathione antioxidant system.
Methods: Primary human osteoarthritic articular chondrocytes were
cultured in 3-D alginate beads in 0%, 1%, 5% or 21% oxygen for 48
hours at pH 7.2 or 6.2 in the absence or presence of IL-1b (10 ng/ml).
Mitochondrial membrane potential was assessed using the fluorescent
dye JC-1. ROS levels were determined by dichlorofluorescein (DCFDA). The reduced glutathione: oxidized glutathione (GSH: GSSG) ratio
was analysed using the GSH/GSSG-Glo½ Assay (Promega).
Results: At pH 7.2, reductions from 5% O2 (normoxia for cartilage
in vivo) to 0% O2 decreased cellular ROS levels by 53%. Acidosis (pH
6.2) increased cellular ROS by 40% (at 5% O2). There was no
difference in ROS levels between 5% and 21% O2 levels at pH 6.2 or
7.2. Addition of IL-1b increased ROS levels in all conditions (except at
0% O2 which was still lower than control levels). Hypoxia (0–1% O2)
decreased GSH: GSSG ratio, mainly by reducing GSH levels. GSH:
GSSG was lowest in acidic (pH6.2) conditions in the presence of IL-1b,
regardless of oxygen tension. Mitochondrial membrane potential
depolarization occurred in hypoxia (mirroring ROS levels) but also
occurred in acidic conditions and in the presence of IL-1b.
Conclusions: These data demonstrate that oxygen tension and pH
are important mediators of mitochondrial function and cellular
antioxidant levels. The conditions that elicited optimal mitochondrial
function were pH of 7.2 at 5% O2. Reductions in ROS levels,
mitochondrial membrane potential and GSH: GSSG ratio were
observed when oxygen tension and pH were lowered, possibly
mimicking the changes in disease where further hypoxia and acidosis
are known features. Addition of IL-1b increased ROS levels in every
condition, (except 0% O2) possibly through inducing a respiratory
burst. A decrease in GSH appears responsible for the decreases in the
GSH: GSSG ratio seen in hypoxic and/or acidic conditions with or
without IL-1b. This work demonstrates the importance of studying
oxygen and pH on mitochondrial function in chondrocytes. The
mechanisms behind this oxygen and pH-sensitivity require further
characterization.
Disclosure statement: All authors have declared no conflicts of
interest.
Wednesday 2 May 2012, 10.45 – 11.45
iii98
Wednesday 2 May 2012, 10.45 – 11.45
Changes in pain/disease activity did not correlate with changes in
synovial volumes, early or static enhancement.
Conclusions: This is one of few DCE MRI studies in OA. Although the
number of participants was small, we demonstrated a reduction in
synovial volume and a significant reduction in total synovial enhancement after IA steroid. DCE MRI will improve our understanding of the
structure-pain relationship in OA and the mechanism of action of
common treatments.
Disclosure statement: All authors have declared no conflicts of
interest.
126. IDENTIFYING THE KEY TARGETS TO IMPROVE
PARTICIPATION IN OLDER ADULTS WITH LOWER LIMB
OSTEOARTHRITIS: PROSPECTIVE COHORT STUDY
Ross Wilkie1, Milisa Blagojevic1, Kelvin P. Jordan1 and
John Mcbeth1
1
Keele University, Keele, United Kingdom
127. ABSOLUTE QUANTIFICATION OF CARTILAGE MATRIX
PROTEINS
Mandy J. Peffers1, Robert J. Beynon2, David J. Thornton3 and Peter
D. Clegg1
1
Institute of Ageing and Chronic Disease, University of Liverpool,
Neston, United Kingdom; 2Proteomics and Functional Genomics
Group, University of Liverpool, Liverpool, United Kingdom;
3
Wellcome Trust Centre for Cell-Matrix Research, University of
Manchester, Manchester, United Kingdom
Background: Osteoarthritis (OA) is characterized by a loss of
extracellular matrix from cartilage (ECM) which is driven by catabolic
cytokines. The composition and structure of the matrix provides the
properties of the cartilage. Cartilage proteomic studies have allowed
the investigation of the functional molecules of cartilage in order to
elucidate the pathogenesis of arthritis. Although proteomics studies of
cartilage and arthritis have increased our understanding of OA and
allowed biomarker discovery few studies have quantified the ECM and
none in absolute terms. Providing formally quantitative data sets will
allow interpretation and parameterization of systems models for OA to
be undertaken. Here we use QconCAT technology which allows
parallel quantification of large sets of analyte proteins, to absolutely
quantify for the first time aggrecan, decorin, biglycan and cartilage
oligomeric matrix protein (COMP) using mass-spectrometry.
Methods: An equine cartilage QconCAT was designed as a
concatenation of tryptic quantotypic peptides using peptides identified
previously. Between two and four peptides were used for each protein
quantified. Genes of these peptides were expressed in E.coli, and
cultured in media supplemented with 13C6 analogues of arginine and
lysine. Full thickness equine articular cartilage was harvested from the
metacarpophalangeal joints of six skeletally mature horses with
grossly normal joints. Cartilage was lyophilized and the soluble
proteins extracted using 4 M guanidine. Analyte and QconCAT were
reduced, alkylated and trypsin-digested in solution on 10000 MWCO
centrifugal concentrators. Samples were desalted using Zip-Tips and
analysed with 10 fmol QconCAT present. The digested peptide mixture
was resolved by LC-MS using a nanoACQUITY chromatograph
coupled to a Waters Xevo-triple quadropole-mass spectrometer.
Quantification was achieved by comparing extracted ion chromatograms of selected y-series ions of heavy (QconCAT) and light (analyte)
transitions. The ratios were normalized to dry weight of cartilage.
Results: Proteins were then quantified with at least two peptides each.
To quantify each peptide a minimum of two transitions were used. For
six donors matrix proteins were quantified as pmol/mg dry weight of
cartilage: aggrecan 8.6 1.19 SEM, biglycan 20.1 5.9SEM, decorin
6.28 1.27SEM and COMP 10.22 1.6SEM.
Conclusions: For the first time we demonstrate the absolute
quantification of matrix protein concentrations in cartilage with
QconCAT technology. Quantification data for the proteins studied
here will enable baseline parameters to be set for cartilage matrix
components and allow study of conditions relating to arthritic
pathology and physiological ageing.
Disclosure statement: All authors have declared no conflicts of
interest.
128. ACTIVATION OF PERIPHERAL TRPV1 RECEPTORS
INDUCES SENSITIZATION OF KNEE JOINT NOCICEPTORS
Rebecca Chapman1,2, Victoria Chapman1, David Walsh1 and
Sara Kelly1,2
1
Arthritis Research UK Pain Centre, University of Nottingham,
Nottingham, United Kingdom; 2Biosciences, University of
Nottingham, Sutton Bonington, United Kingdom
Background: Peripheral sensitization contributes to pain in knee
osteoarthritis (OA). Peri-patellar pain thresholds are lowered in human
knee OA and knee joint afferents are sensitized in the monosodium
iodoacetate (MIA) rat OA pain model. Sensitization mechanisms are
not well understood. TRPV1 (transient receptor potential vanilloid)
expression increases in knee joint afferents in the MIA model. We have
reported that peripheral administration of JNJ-17203212 (TRPV1
antagonist), reversed MIA-induced knee joint afferent sensitization.
Here we investigated whether activating TRPV1 receptors with the
agonist capsaicin could mimic MIA-induced sensitization of knee
afferents under normal conditions and / or enhance MIA-induced
sensitization.
Methods: Male Sprague-Dawley rats (175–200 g) were injected (left
knee) with MIA (1 mg/50ml, n ¼ 10) or saline (50 ml, n ¼ 11). 14 days
post-injection rats were anaesthetized with sodium pentobarbital
(60 mg/kg, i.p.) and the external jugular vein, trachea and femoral
artery were cannulated. Extracellular recordings were made from knee
joint-associated afferents (receptive fields (RF) overlying the knee joint)
in response to von Frey monofilament stimulation (0.4–15 g, 5 s each/
5 min). Once stable control evoked responses were obtained,
Capsaicin (5, 10mM; Tocris) or vehicle (100 ml 2.5, 5% ethanol) was
injected (close i.a) and effects followed at 5 min intervals for 60 min.
Conduction velocities were estimated (RF electrical stimulation;
range ¼ 0.45-31.5 ms-1; A- and C-fibres.
Results: In 56% of knee afferents in saline rats, peripheral capsaicin
facilitated (sensitized) mechanically evoked responses (p < 0.001,
ANOVA); capsaicin was not able to further sensitize responses in
MIA rats. In 58 and 44% of knee afferents in MIA and saline rats
respectively, peripheral capsaicin significantly inhibited (desensitized)
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: Up to 97% of older adults with osteoarthritis have
additional comorbid health problems. Multimorbidity (3 þ health
problems) predicts a poor outcome including restricted participation,
however the pathways are complex. Identifying the mechanisms that
increase the risk of restricted participation and factors which are
amenable to change will inform future management and prevention
strategies. Combining a conceptual approach (the ICF framework) and
previous research, the objective was to test theoretical mechanisms
and estimate the extent that modifiable factors contribute to the path
from multimorbidity to onset of restricted participation.
Methods: The study was nested within a population-based prospective cohort study (the North Staffordshire Osteoarthritis Project).
Subjects were 383 patients aged 50 and over who had consulted a
general practitioner for lower limb osteoarthritis and were free of
restriction at baseline. Path analysis was used to estimate the
contribution of putative mediators (severe lower limb joint pain,
obesity, depression and locomotor disability at three years) on the
link between multimorbidity at baseline and onset of restricted
participation at 6 years by determining the proportion of the total
direct effect (expressed as odds ratio (OR) with 95% confidence
interval (CI)) of multimorbidity on onset explained by each mediating
factor.
Results: 103 (28%) participants indicated the onset of restricted
participation at six year follow-up. Multimorbidity at baseline was
associated with the onset at six years (OR 3.55; 95%CI 2.21, 5.72)
without adjustment for the assessed factors. Adding only obesity to
the model explained 11% of the total effect of multimorbidity on onset
of restriction at 6 years. Adding just severe lower limb joint pain
explained 24%.However, further addition to the model of depression
and locomotor disability increased the total proportion explained of the
effect of multimorbidity on onset but reduced the proportion explained
individually by obesity and lower limb pain severity. Locomotor
disability explained the greatest proportion of the effect of multimorbidity on the onset of restricted participation (e.g. locomotor
disability and severe lower limb joint pain explained 79%; pain
explained 5.5%, whilst locomotor disability explained 74%). Inclusion
of all four factors explained 94% of the total effect of multimorbidity on
onset of restricted participation at 6 years.
Conclusions: Obesity, lower limb joint pain, depression and locomotor disability explained almost all of the effect of multimorbidity on the
onset of restricted participation. Locomotor disability and depression
made the strongest contribution and are key targets for clinical
interventions. The results suggest that even when the symptoms of
osteoarthritis, multimorbidity and obesity exist, participation may be
improved through the management of depression and locomotor
disability.
Disclosure statement: All authors have declared no conflicts of
interest.
POSTER VIEWING II
POSTER VIEWING II
mechanically evoked responses (p < 0.001, ANOVA). Vehicle had no
effect in either saline or MIA rats.
Conclusions: These data suggest that activation of peripheral TRPV1
receptors is able to induce mechanical sensitization in a proportion of
joint afferents in saline control rats. Following peripheral capsaicin in
MIA rats, joint afferents did not further sensitize and a higher
proportion than in saline rats exhibited desensitization. We postulate
that joint afferents in MIA rats may be maximally sensitized via TRPV1mediated mechanisms and that existing endogenous TRPV1 activation
(e.g. by endovanilloids) may increase the likelihood of desensitization.
TRPV1 appears to be important in the maintenance of sensitization of
knee joint afferents and may be a potential therapeutic target in
treating OA pain.
Disclosure statement: All authors have declared no conflicts of
interest.
129. PATTERNS OF HIP MIGRATION IN OSTEOARTHRITIS
OF THE HIP
Background: Variations in the pattern of femoral head migration in hip
osteoarthritis (OA) was initially described by Resnick in 1975. The
reasons for different patterns are unclear. Genetic and constitutional
factors have been suggested, supported by the finding that hand
nodes (Heberden’s and Bouchard’s) associate with large joint OA. This
study aims to assess whether the pattern of hip migration is associated
with factors such as nodal status and age of onset, and whether there
are differences between the first and second hip affected in bilateral
hip OA.
Methods: Participants included men and women with OA of the hip
recruited between 2002 and 2006 as part of the Genetics of
Osteoarthritis and Lifestyle (GOAL) and Genetics of Osteoarthritis
(GOA) studies. Anteroposterior views of the pelvis were obtained using
a standardized protocol. Hip OA was defined radiographically as the
presence of definite joint space narrowing and definite osteophytes,
equivalent to a Kellgren-Lawrence score of 2. The area of maximal
joint space narrowing was recorded as superolateral, superior
intermediate, superomedial, superior indeterminate, axial migration,
medial migration or concentric. Nodal phenotype was defined clinically
as Heberden’s and/or Bouchard’s nodes affecting at least 2 rays of
each hand.
Odds ratios (OR) and 95% confidence intervals (CI) were calculated
for association. Logistic regression models were used to adjust for
confounding factors including age, gender and body mass index (BMI).
Results: 1438 cases of hip OA were identified (52.9% female), with a
mean age of 68.7 (range 45 to 90), and mean BMI 29.1 (range 14.5 to
58.5). 437 (30.4%) had the nodal phenotype. Bilateral hip OA was
present in 651 (45.3%). Crude OR suggested a negative association
between nodal phenotype and superior intermediate migration of the
hip, but a positive association with superomedial and axial patterns.
However, this association was lost after adjustment for age, gender
and BMI. However, the age of symptom onset of hip OA was
associated with superolateral migration (OR 1.65, 95% CI 1.03-2.66,
p ¼ 0.039) in people age between 41 and 50, and superomedial
migration (OR 2.24, 95% CI 1.40-3.59, p ¼ 0.001) in those aged 70
years after adjustment for gender and BMI. In those with bilateral hip
OA, the second hip was more likely to be of superolateral pattern (OR
0.68, 95% CI 0.50-0.93, p ¼ 0.014) after adjustment for age, gender
and BMI. Conversely, the first hip was likely to be of superomedial
migration (1.72, 95% CI 1.21-2.45, p ¼ 0.003).
Conclusions: In contrast to predicted, nodal phenotype does not
correlate with the pattern of femoral head migration in hip OA.
However, the age of symptom onset suggests that a more lateral
migration is found in younger patients compared with a more medial
migration in older patients. In bilateral hip OA, second hips affected
appear to be more lateral than first hips, which may be explained by
biomechanical changes on the second hip.
Disclosure statement: R.M. owns stock or stock options in
AstraZeneca. All other authors have declared no conflicts of interest.
130. DKK3 CAN PREVENT CARTILAGE DEGRADATION AND
REGULATE CHONDROCYTE CELL SIGNALLING
Sarah Snelling1,2, Rose K. Davidson1, Tracey Swingler1,
Andrew Price2 and Ian Clark1
1
BMRC, The University of East Anglia, Norwich, United Kingdom;
2
NDORMS, University of Oxford, Oxford, United Kingdom
iii99
Background: We have previously shown that Dkk3 expression is
increased in OA cartilage and synovium. Levels of Dkk3 in synovial
fluid are also increased in individuals with tricompartmental OA and
after arthroscopy. The factors regulating Dkk3 expression in cartilage
and the effect of Dkk3 on chondrocyte function are poorly ascribed.
Correct regulation of cell signalling pathways is integral to cartilage
homeostasis and thus the prevention of OA pathogenesis. Dkk3 is a
member of the Dkk family of Wnt antagonists and therefore may
impact on chondrocyte biology through interaction with the Wnt
pathway. Dkk3 has also been found to influence TGFb signalling in
other cell systems.
Methods: Expression of Dkk3 was assessed in primary human
articular chondrocytes (HAC) following treatment with interleukin-1
(IL1) and oncostatin-M (OSM). The effect of Dkk3 on IL1/OSM-induced
proteoglycan and collagen release from explants of bovine nasal
(BNC)- and primary human-cartilage was assessed. SW1353 chondrosarcoma cells were treated with Dkk3þ/-Wnt3a, TGFb and Activin
and TOPFlash and CAGA luciferase reporters used to measure Wnt
and Smad signalling. RNA was extracted from primary HAC treated
with Dkk3þ/-TGFb or Wnt3a. ADAM12 and TIMP3 expression were
measured to assess TGFb signalling and AXIN2 to assess Wnt
signalling. Dkk3 was silenced in primary HAC for microarray analysis.
Results: Dkk3 expression was decreased in primary HAC following
IL1/OSM treatment. In BNC explants, IL1/OSM-induced proteoglycan
release was inhibited by Dkk3. Dkk3 antagonized Wnt signalling,
decreasing Wnt3a-induced AXIN2 expression and luciferase expression from the TOPFlash reporter. Interestingly, Dkk3 enhanced TGFb
signalling, increasing TGFb-induced TIMP3 and ADAM12 expression
and TGFb-induced luciferase from the CAGA-luc reporter. In contrast
Dkk3 antagonized Activin-induced CAGA-luc activity, TIMP3 and
ADAM12 expression. Knockdown of Dkk3 in primary HAC resulted in
altered expression of a number of genes, with decreases in DICER and
BMPR2, and increases in CTGF detected.
Conclusions: OA pathogenesis is likely regulated by a multitude of
factors relating to cell signalling including the balance of cytokines in
the articular joint. Dkk3 expression is increased in OA but can be
regulated IL1 and OSM. This suggests a balance of Dkk3 effects
depending upon the biological stimuli within the cartilage. Dkk3 may
act in a protective role in the presence of inflammatory cytokines as
exemplified by its ability to inhibit matrix loss. Dkk3 knockdown
decreases DICER expression and thus changes in Dkk3 expression in
OA may alter chondrocyte phenotype through alterations in miRNA
activity. The ability of Dkk3 to antagonize Wnt, enhance TGFb and
antagonize Activin signalling would have multiple effects on chondrocyte activity. These results imply that Dkk3 could influence multiple
OA-relevant processes, protect cartilage from degradation and be
important in cartilage development and homeostasis.
Disclosure statement: All authors have declared no conflicts of
interest.
131. SUPRASPINAL CHANGES IN NEURONAL AND GLIAL
CELLS IN ANIMAL MODELS OF OSTEOARTHRITIC PAIN
Elizabeth Stockley1, Gareth Hathway1, Henryk Faas2,
Dorothee Auer2 and Victoria Chapman1
1
School of Biomedical Science, University of Nottingham,
Nottingham, United Kingdom; 2Academic Radiology, University of
Nottingham, Nottingham, United Kingdom
Background: Animal models of osteoarthritis (OA) exhibit structural
changes to the joint, and are associated with the development of
allodynia and hyperalgesia. Nociceptive processing induces phosphorylation of extracellular signal-regulated kinase (pERK) and the
expression of the early immediate gene c-fos in the central pain
pathways. Non-neuronal glial cells (microglia and astrocytes) are also
associated with chronic pain states. Positive immuno-staining against
glial fibrillary acidic protein (GFAP) and ionized calcium binding
adaptor molecule 1 (IBA1) in astrocyte and microglia respectively, in
conjunction with a change in morphology, is a widely used marker of
glial activation. Here, immunohistochemistry against pERK, cFos,
GFAP and IBA1 was used to identify neuronal activity and glial
activation in supraspinal areas in a model of OA pain.
Methods: Intra-articular injection of sodium mono-idoacetate (MIA)
was used to produce experimental OA in male adult Sprague-Dawley
rats. The development of pain behaviour as changes in hind limb
weight bearing and mechanical withdrawal thresholds were assessed.
After 3, 7, 14 and 28 days post- injection, fixed brainstem and
forebrain tissue was removed and sectioned for free floating
immunohistochemistry.
Results: MIA treatment produced a marked decrease in mechanical
withdrawal threshold and changes in hind limb weight bearing at all
time points studied. No change in cFos or pERK expression was seen
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Michelle Hui1, Weiya Zhang1, Sally Doherty1, Frances Rees1,
Kenneth Muir1, Rose Maciewicz2 and Michael Doherty1
1
Academic Rheumatology, University of Nottingham, Nottingham,
United Kingdom; 2AstraZeneca, Macclesfield, United Kingdom
Wednesday 2 May 2012, 10.45 – 11.45
iii100
Wednesday 2 May 2012, 10.45 – 11.45
in brainstem or forebrain regions, including the rostral ventral medial
medulla (RVM), dorsal PAG and cingulate cortex in MIA treated rats,
compared to saline treated rats. However, there was an increase in the
number of GFAP stained astrocytes, in MIA treated animals, at both 14
days (208.6 24.0 vs 166.3 17.6 MIA vs saline, mean SEM) and 28
days (237.8 17.2 vs 179.5 20.8 MIA vs saline, mean SEM) posttreatment. In addition, the number of activated microglia also
increased in the RVM at day 28 (59 4.7 vs 3.8 1.6, MIA vs saline,
mean SEM) post-treatment.
Conclusions: In conclusion, the MIA model of OA produces chronic
pain behaviour which is associated with the activation of glial cells in
regions of the brainstem which mediate descending controls to the
spinal cord.
Disclosure statement: All authors have declared no conflicts of
interest.
132. PSYCHOLOGICAL FACTORS INCLUDING ILLNESS
PERCEPTIONS MAY PREDICT RESPONSE TO
CORTICOSTEROID INJECTION IN OSTEOARTHRITIS
Background: Intra-articular corticosteroid injections are commonly
used to treat pain in patients with arthritis of the knee, but little is
known about factors that govern response to injection. As part of an
observational pilot study of injections in knee arthritis, we aimed to
determine the relevance of psychological characteristics in predicting
the response to injections.
Methods: 32 patients underwent knee injection with triamcinolone and
lignocaine as part of an observational study. 23(71%) were female.
Mean age was 63.4 (35–80). 21 had primary osteoarthritis and 11
rheumatoid arthritis with radiographic change, in whom symptoms
were attributed to degenerative rather than inflammatory disease.
Response to injection between baseline and 3 weeks was assessed by
WOMAC osteoarthritis index and global VAS. The primary outcome
measure was 40% fall in WOMAC pain subscale and secondary
outcome was OARSI response (50% improvement in pain, function or
global subscales or 20% improvement in 2/3 domains). Apart from
demographic and physical factors, such as age, body mass index,
symptom duration and presence of effusion, as defined by ultrasound,
we examined the following psychological factors: depression and
anxiety,using AIMS2 subscales, pain catastrophizing, using the Pain
Catastrophizing Scale(PCS) and patients’ illness perceptions using the
Personal Control(PC)and Treatment Control(TC) subscales of the
revised Illness Perception Questionnaire(IPQR), a validated questionnaire assessing patients’ beliefs about their illness.
Results: Improvement in pain, stiffness and function subscales
and global VAS were significant at week 3 (p < 0.005, < 0.001,
< 0.005, < 0.001 respectively). 16 patients (50%) were classified as
WOMAC responders and 22 (69%) as OARSI responders. Univariate
analysis was performed between responder status and psychological
subscales (as high/low subscale groups, dichotomized at median). A
high score for TC subscale (19; possible range 5-25) was significantly
associated with both WOMAC response (p ¼ 0.0061, OR 9.0, 1.816 to
44.61) and OARSI response (P ¼ 0.027, OR 7.0, 1.184 to 41.38). A
lower PCS score (<15, possible range 0-52) showed a trend towards
OARSI response (p ¼ 0.08). No significant associations were found
between responder status and diagnostic group, age, duration of
disease, BMI or presence of effusion. There was no significant
association between rate of previous steroid injection or recalled
benefit (by VAS) and responder status.
Conclusions: The results of our pilot study suggest that patients who
believe their condition is more modifiable by treatment are more likely
to report a positive outcome following intra-articular corticosteroid
injection for knee arthritis. This observation appears independent of
whether they had previous injections or recalled degree of benefit
associated. By contrast, neither presence of effusion nor simple
demographic factors were associated with response in this sample.
Disclosure statement: All authors have declared no conflicts of
interest.
133. LIFECOURSE PREDICTORS OF ULTRASOUND
FEATURES OF HIP OSTEOARTHRITIS: THE NEWCASTLE
THOUSAND FAMILIES STUDY
Ajay Abraham1, Mark S. Pearce1, Kay D. Mann1, Roger M. Francis2
and Fraser Birrell3
1
Institute of Health and Society, Newcastle University, Newcastle
upon Tyne, United Kingdom; 2Institute for Ageing and Health,
Newcastle University, Newcastle upon Tyne, United Kingdom;
3
Musculoskeletal Research Group, Institute of Cellular Medicine,
Newcastle University, Newcastle upon Tyne, United Kingdom
Background: There has been very little lifecourse research looking at
the risk of osteoarthritis (OA). We performed a lifecourse analysis of
risk factors for hip OA (defined by osteophytes and femoral head score
on ultrasound) acting at different stages of life, among members of the
Newcastle Thousand Families birth cohort.
Methods: Participants from the cohort aged 63 years (born in MayJune 1947), had both hips scanned by a trained musculoskeletal
sonographer. Potential risk factors for hip OA (including birth weight
and breast feeding data) were collected prospectively in this birth
cohort and an a priori conceptual framework was developed.
Ultrasound protocols were derived from EULAR guidelines. Hip OA
was considered to be present if an osteophyte or femoral head
abnormality was identified. These data were analysed in relation to a
range of factors from across the lifecourse using logistic regression
models.
Results: 304 participants were scanned; 56% women, mean BMI was
27.9 kg/m2(sd ¼ 4.9). Prevalence of hip OA was 26%, 30% and 41%
for right, left and ‘‘any’’ hip, respectively. The final multivariate model
identified three risk factors for hip OA; BMI at age 50 was the strongest
predictor (OR 1.11; 95% CI 1.04, 1.18; p ¼ 0.003) followed by
occupational and housework related physical activity (OR 1.48; 95%
CI 1.11, 1.98; p ¼ 0.008) and pack years of smoking (OR 1.02; 95% CI
1.00, 1.05; p ¼ 0.02). A borderline univariate inverse association was
found between educational status and hip OA (OR 0.46 graduate
versus school dropout; 95% CI 0.20, 1.02) but this association was
found to be mediated by the effect of educational status on
subsequent smoking patterns and physical activity. Among men,
increased height (OR 0.88 per cm; 95% CI 0.81, 0.97) was protective
while the occurence of an adverse life event (OR 3.15; 95% CI 1.18,
8.41) increased risk of hip OA. The risk of hip OA in women increased
with percentage body fat (OR 1.06; 95% CI 1.01, 1.10), levels of
physical activity (OR 1.55; 95% CI 1.00, 2.39) and low levels of vitamin
D intake (OR 0.78 per mcg/day; 95% CI 0.61, 0.98).
Conclusions: This is the first study to perform a lifecourse analysis of
hip OA risk using prospectively collected data. Obesity and occupational physical activity are recognized risk factors for hip OA, while the
positive association of smoking with hip OA in this study is a novel
finding. The mechanisms for this association of smoking with hip OA
might be due to immunological insults leading to an inflammatory
phenotype of OA or its deleterious effects on adipocytokines and
oestrogen. There were marked differences in risk factor profiles
between the sexes. These results demonstrate that risk factors acting
in adulthood play a greater role than those acting in early life. This
would suggest that public health interventions aimed to reduce the
burden of hip OA should focus on lifestyle modification in adulthood.
Disclosure statement: All authors have declared no conflicts of
interest.
134. PILOT STUDY TO ASSESS THE VALIDITY OF A SIMPLE
ACCELEROMETRIC METHOD TO ASSESS HEEL STRIKE
TRANSIENTS IN PATIENTS WITH MEDIAL KNEE JOINT
OSTEOARTHRITIS
Marian Tucker1, Stephen J. Mellon1, Luke Jones1, Andrew J. Price1,
Paul A. Dieppe2 and Harinderjit S. Gill1
1
NDORMS, University of Oxford, Oxford, United Kingdom;
2
Peninsula College of Medicine & Dentistry, Universities of Exeter &
Plymouth, Exeter, United Kingdom
Background: Impact forces of the heel on initial ground contact during
walking produce transient stress waves that transmit through the lower
extremities. This transient behavior can be measured in ground
reaction force and is known as the heel strike transient (HST).
Studies have shown that an association may exist between the level
of these impulsive forces and articular and joint degenerative process.
The purpose of this study was to assess whether HST measured in
ground reaction forces correlate with 3-axis acceleration measurements taken at the ankle.
Methods: Twelve subjects participated in this study, approved by the
local ethics committee. Seven subjects with radiographic OA (K&L 2 or
more) and symptomatic (chronic pain in that knee) were tested
alongside 5 age-matched controls without knee pain. Each patient
underwent motion analysis at the Oxford Gait Laboratory using a
VICON MX system (Vicon, Oxford, UK). Reflective markers were
placed on each subject’s pelvis, ankles and feet. Each participant also
wore two 3-axis accelerometers, built in-house, on rigid ankle cuffs.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
George Hirsch1,2, Elizabeth Hale1, George Kitas1,2 and
Rainer Klocke1,2
1
Clinical Research Unit, Dudley Group NHS Foundation Trust,
Dudley, United Kingdom; 2Arthritis Research UK Clinical
Epidemiology Unit, University of Manchester, Manchester, United
Kingdom
POSTER VIEWING II
POSTER VIEWING II
135. INCREASED SENSITIVITY TO NERVE GROWTH FACTOR
IN THE MONOSODIUM–IODOACETATE MODEL OF
OSTEOARTHRITIS
Sadaf Ashraf1, Victoria Chapman1 and David A. Walsh1
1
Arthritis Research UK Pain Centre, University of Nottingham,
Nottingham, United Kingdom
Background: Osteoarthritis (OA) is often characterized by episodes of
increased pain with associated synovitis. The origin of pain in OA is
poorly understood. Nerve growth factor (NGF) levels are increased in
the OA joint, and during inflammation. Pain flares may be due to either
increased release, or to increased sensitivity to NGF. We hypothesized
that synovitis in the osteoarthritic joint may lead to a sustained and
enhanced increase in NGF-induced pain behaviour. Our aim was to
find out whether pain behaviour induced by intra-articular injection of
NGF is increased in the MIA model of OA and if this enhanced
response to NGF is due to synovial inflammation during the
development of OA.
Methods: OA was induced in left knee joint on day 0 in male Sprague
Dawley rats (n ¼ 8 animals/group) weighing approximately 200 g by
intra-articular injection of 1 mg of MIA in 50 ml saline. Saline injected
animals were used as non-arthritic controls. Intra-articular injection of
NGF (10 mg/50ml) or saline control was given in the left knee joint when
OA pathology had fully established (day 20). Indomethacin (2 mg/kg,
daily, orally) or saline control was given from before induction of OA
(day -1) to day 18, followed by a 2 day washout period before NGF
injection. Joint tissues were harvested 7 days following NGF injection.
Synovial inflammation was measured as the macrophage fractional
area (% synovium occupied by ED1 þ ve cells), thickness of the
synovial lining and joint swelling. Pain behaviour was measured as
hind-limb weight-bearing asymmetry.
Results: Pain behaviour was increased following induction of OA. Pain
behaviour of indomethacin-treated osteoarthritic animals was reduced
to saline injected control levels by day 18 whereas vehicle-treated
arthritic controls still showed an increase in pain behaviour. Intraarticular injection of NGF in OA animals was followed by an enhanced
and sustained pain-response compared with that observed in nonarthritic controls. Indomethacin pre-treatment significantly inhibited
the pain behavioural response to intra-articular NGF injection in OA
knees compared to vehicle treated arthritic controls. Synovial
inflammation 2 days after discontinuation of indomethacin (day 20,
prior to NGF injection) was not significantly reduced compared to
vehicle treated animals.
Conclusions: NGF-induced pain behaviour is increased and sustained
in the MIA model of OA. Low level inflammation may contribute to this
enhanced pain response, as it was partially reduced by pretreatment
with indomethacin. However, reduced pain response to NGF was
observed despite persistent synovitis after indomethacin withdrawal,
and involvement of other factors such as effects of indomethacin on
pain processing deserves further investigation.
Disclosure statement: All authors have declared no conflicts of
interest.
iii101
OSTEOPOROSIS AND METABOLIC
BONE DISEASE
136. THE IMPACT OF COMPLEX REGIONAL PAIN
SYNDROME TYPE 1 ON BONE MINERAL DENSITY
David McCollum1, Candy McCabe2,3, Sharon Grieve3,
Jacqueline Shipley4 and Rachel Gorodkin5
1
Undergraduate Medicine, University of Manchester, Manchester,
United Kingdom; 2Faculty of Health and Life Sciences, University of
the West of England, Bristol, United Kingdom; 3Bath Centre for Pain
Services, Royal National Hospital for Rheumatic Diseases, Bath,
United Kingdom; 4Clinical Measurement, Royal National Hospital for
Rheumatic Diseases, Bath, United Kingdom; 5Kellgren Centre for
Rheumatology, Manchester Royal Infirmary, Manchester, United
Kingdom
Background: Sudeck first described the presence of localized
osteoporosis in what is now known as complex regional pain
syndrome (CRPS) in 1900. Studies have since described the typical
pattern of patchy osteoporosis seen in patients with CRPS, but very
little work has been done to characterize this further. The aim of this
study was to determine if bone mineral density (BMD) was reduced in
the affected limb of patients with CRPS when compared to the
contralateral asymptomatic limb.
Methods: 44 patients with CRPS type 1 who met the IASP 1995
criteria underwent whole body dual-energy x-ray absorptiometry (DXA)
scanning (HologicÕ Discovery A model) as part of routine work-up.
BMD was compared between the affected and contralateral asymptomatic limbs. Analysis was conducted using Wilcoxon Signed Ranks
test. Exclusion criteria were those with bilateral upper or lower limb
CRPS and those with metallic prostheses or metallic jewellery in/on
either limb at the time of their DXA scan.
Results: Data from 44 CRPS patients (38 female, 18 upper limb, 27
lower limb) were analysed, which included 45 limbs in total as one
patient had both upper and lower limb CRPS. Median age at onset
was 49.5 (IQR 39-56) years and median disease duration was 2 (IQR 13) years.
There was no statistically significant difference in BMD between the
affected and contralateral unaffected limbs in patients with CRPS
(p ¼ 0.116; see Table 1). When upper and lower limb cases were
analysed separately, there was no significant difference between the
affected and contralateral unaffected limbs in the upper limb cases
(p ¼ 0.778), but BMD was significantly lower on the affected side
than the contralateral asymptomatic side in the lower limb cases
(p ¼ 0.032).
Conclusions: This is the largest study to date looking at the
association between BMD and CRPS. Unlike previous studies, we
have not shown any significant difference in BMD in the overall group
or between upper limbs, but there is a significant difference between
lower limbs. A possible reason for this includes the relatively greater
effect in the lower limbs of non-weight bearing on the painful limb.
Study limitations include the relatively small number of subjects;
measurement of BMD in the entire limb when only one localized area
might be affected by CRPS; a lack of population control data for whole
body DXA; and possible issues with differential BMD depending on
limb dominance. Future work will include the analysis of standard hip
DXAs in patients with lower limb CRPS, which will allow comparison
against a large reference group with T and Z scores and will further
elucidate the results of this study.
TABLE 1 Comparison of median (IQR) BMD (g/cm2) between affected and
contralateral asymptomatic limbs
Upper limb (n ¼ 18)
Lower limb (n ¼ 27)
Both upper and lower
limb (n ¼ 45)
Affected limb
Contralateral
asymptomatic
limb
P value
0.762 (0.691– 0.814)
1.138 (1.056– 1.191)
1.034 (0.773–1.171)
0.747 (0.729–0.803)
1.143 (1.104–1.169)
1.081 (0.765–1.145)
0.778
0.032
0.116
Disclosure statement: All authors have declared no conflicts of
interest.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Subjects were then asked to walk barefoot at their self selected normal
walking pace. Ground reaction forces were recorded using three force
platforms; two AMTI OR6-1-1000 and an AMTI OR6-6-1000 (AMTI,
MA, USA). Synchronized ground reaction forces and acceleration data
were recorded at 1000 Hz. Post-processing was performed in Matlab
(The MathWorks Inc., Natick, MA, USA).The mean vertical deceleration
at HST was calculated for each group and compared with a Mann
Whitney-U test. The correlation between peak vertical ground reaction
force and peak vertical acceleration was also assessed using the
Pearson product-moment correlation coefficient using PASW
Statistics 18 (IBM, Armonk, NY, USA).
Results: The mean deceleration for the OA group was 3.1 g ( 1.6) and
the mean deceleration for the control group was 1.8 g ( 2.4). There
was no statistical significant difference these values. However, peak
vertical ground reaction force showed a correlation with vertical
acceleration for all subjects. This correlation was found to be
statistically significant (p ¼ 0.015, pearson corr coef ¼ -0.707).
Conclusions: The results of this study suggest it is possible to assess
HST using 3-axis accelerometers rigidly attached to the ankles. The
ability to detect and measure HST using accelerometry could have an
application in the investigation of joint pathogenesis in OA.
Accelerometers could have a use in biofeedback device for control
of joint pain.
Disclosure statement: All authors have declared no conflicts of
interest.
Wednesday 2 May 2012, 10.45 – 11.45
iii102
Wednesday 2 May 2012, 10.45 – 11.45
137. INCREASING AGE IS ASSOCIATED WITH DECREASED
FEMORAL NECK CROSS-SECTIONAL MOMENT OF INERTIA
IN FEMALES ONLY: A POSSIBLE FACTOR IN AGE- AND
SEX-RELATED FRACTURE RISK
Alexander G. Oldroyd1,2, Bronwen Evans2, Cathi Greenbank2 and
Marwan Bukhari2,3
1
School of Health and Medicine, Lancaster University, Lancaster,
United Kingdom; 2Rheumatology, Royal Lancaster Infirmary,
Lancaster, United Kingdom; 3School of Clinical Sciences, University
of Liverpool, Liverpool, United Kingdom
138. OSTEOPOROSIS SCREENING AND MANAGEMENT IN
PATIENTS COMMENCING AROMATASE INHIBITORS FOR
BREAST CANCER
Rizwan Rajak1, Cheryl Bennett1, Ann Williams1 and James C. Martin1
1
Rheumatology, Royal Glamorgan Hospital, Llantrisant, United
Kingdom
Background: Current treatment of postmenopausal women diagnosed with breast cancer whose tumour expresses hormone receptors
is with aromatase inhibitors(AI). AIs deplete oestrogen by inhibiting
aromatase, an enzyme which synthesizes oestrogen from androgens,
causing increased bone turnover and accelerated bone loss; this
occurs at an average rate of 1-3% per annum. Subsequently, the
incidence of osteoporotic fractures has increased in patients using
these treatments necessitating baseline bone density assessment
using densitometry scanning(DXA) on commencement of AIs. In fact,
the rate of bone loss and fracture risk associated with AIs is significant
enough to lower the threshold for anti-bone resorptive agents to a T
score of 2.0 compared with 2.5 in postmenopausal osteoporosis.
We conducted an audit to assess whether patients receiving AI’s have
been appropriately screened and managed for osteoporosis(OP).
Methods: Patients from Cwm Taf Health Board started on AIs was
obtained via our pharmacy prescribing database. Data was collected
retrospectively on patients treated with AIs between Jan‘08-Jan‘11.
Audit outcomes entailed (a)appropriate screening for OP, (b)appropriate treatment of OP & (c)incidence of OP/osteopenia. Appropriate
management was defined as compliance with the collaborative
guidance by the UK expert group 2008.
Results: Of 384 patients started on AIs, only 81(21%) had been
referred for DXA & OP risk factor assessment. Of the 81 cases, 32%
were referred by primary care, 26% breast oncologists & 42% breast
surgeons. Mean time between commencement of AI and DXA was 13
months; only 40% had had their DXA at 6 months after starting an AI.
Osteopenia was diagnosed in 43% and OP in 30%; in those with OP
only 1 case was assessed for secondary causes of OP. 88% of all
cases received bone supplementation. Bisphosphonates were prescribed in <1/3 of osteopenic patients and all but 2 OP patients. 11%
of the cohort were >75years with 1 OP risk factor;none were
assessed further for secondary OP but all were on appropriate
treatment. Of the patients who had a T-score <-1.0 none had a repeat
DXA arranged within 24 months.
Conclusions: OP in patients treated with AIs is common, found in 1/3
of the audited cohort that were screened. Worryingly, the vast number
of patients who have been commenced on AIs in the CwmTaf
region(South Wales) have not been appropriately screened for OP
likely leading to an underestimation of disease and those requiring
treatment. The key areas at fault are initial referral for DXA, obtaining
DXAs within 3-6 months and assessment of secondary OP.
Conversely, the majority of those who were assessed were initiated
on the correct bone protection regime. With the increasing burden of
OP associated with AIs in breast cancer and the availability of clear
guidance on how to screen and manage these patients, more effort is
required to disseminate awareness regarding this to health professionals involved in breast cancer care.
Disclosure statement: All authors have declared no conflicts of
interest.
139. IMPROVING REFERRAL RATE OF VERTEBRAL
FRACTURES TO FRACTURE LIAISON SERVICE: A SERVICE
EVALUATION
Rita Abdulkader1, Carolyn MacNicol1, Karen Brixey1,
Sonya Stephenson1 and Gavin Clunie1
1
Rheumatology, The Ipswich Hospital NHS Trust, Ipswich, United
Kingdom
Background: Patients with vertebral fractures (VFs) are not well
represented in Fracture Liaison Services (FLSs) owing to factors such
as late presentation and low detection rates. Only 16 patients were
referred to our FLS clinic with VFs between January and June 2010
.We report here the results of a pilot scheme that ran over a similar
period in 2011 that aimed to improve referral rates of VFs to FLS.
Methods: The radiologists agreed to copy spinal radiograph reports of
VFs to our FLS and advise the referrers to do an ‘osteoporosis risk
assessment’ where ‘osteopenia’ alone was reported. Additionally an
FLS radiographer reviewed all reports on ‘Back X-Rays’ each week to
cross-referencing the process. For fracture reports, patients <80y old
were invited to FLS if no recent osteoporosis assessment had been
done, and there was no known severe pathology which made further
assessment inappropriate (e.g. terminal illness). Patients 80y old
were referred to a community nurse (CN) who facilitated a fracture risk
assessment and advised GP on management. The CN also facilitated
a risk assessment for all patients with reported osteopenia.
Results: 281 reports of either VFs or osteopenia were identified. 157/
281 (56%) patients were <80y old and 1 VFs were reported in 91/157
(58%). Only 26/91 (29%) reports were sent to our FLS by the Radiology
Department. The rest (65) were identified by us. Invitations to FLS were
sent to 75/91 (82%), of whom 63 (84%) attended, 25/63 (40%) were
started on osteoporosis treatment (25/91 [27%] of the original fracturereported group). Of the other 38/63 (60%), existing treatment was
replaced in 3 and continued in 21. Of the 124 patients 80y old, 80
were reported to have VFs, but only 6 reports were sent to FLS. The
CN contacted these patients and found that 57/80 (71%) were already
on osteoporosis treatment—but often adherence was poor. After
assessment, treatment was started in 7/23 (30%) patients; the rest
declining treatment or further assessment was unsuitable. 110 patients
were reported to have osteopenia; 66/110 (60%) were <80y old. Of
these, 27/110 (25%) were already on treatment. After assessing the
remaining 83 patients, the CN started treatment in 14.
Conclusions: We report a service which promptly identifies a
substantial number of patients with VFs. As a result, in 6 months, 46
new patients were identified at high risk of osteoporotic fracture and
started on therapy, this was 3 times the previous detection rate. We
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: Studies have shown a link between increasing age and
detrimental changes to the shape of the proximal femur. Studies have
shown that age-related femoral neck cortical thinning is more
pronounced in women; this may contribute to differences of agerelated fracture risk between men and women. This study aimed to
investigate for differences between age-related changes in proximal
femur shape in men and women.
Methods: Dual X-ray Absorptiometry scan results of patients referred
to a DGH between 1996 and 2010 were used. The following was
recorded: age, sex, body mass index (BMI), previous femoral neck
fragility fracture status, hip structural analysis (HSA) measurements
were collated: distance from centre of femoral head to centre of
femoral neck (d1), distance from centre of femoral head to intertrochanteric line (d2), mean femoral neck diameter (d3), distance from
centre of mass of femoral neck to superior neck margin (y), hip axis
length (HAL), proximal femur strength index (SI) and cross-sectional
moment of inertia (CSMI) - a measurement of optimal femoral neck
bone distribution. Generalized linear modelling, adjusted for BMI, was
used to model significant associations between age and each HSA
measurement. Analysis was carried out for men and women
separately. Logistic regression modelling, adjusted for BMI was used
to model any significant association between previous femoral neck
fracture status and age in the female and male cohorts separately.
Results: Data of 12391 (83.95% female) subjects were analysed. For
females and males, respectively, the mean age was 64.07 years (SD
12.41) and 65.32 years (SD 13.05), mean BMI was 26.71 kg/m2 (SD
5.41) and BMI 26.99 kg/m2 (SD 4.67). For females (coefficient), age
was significantly negatively associated with d1 (-0.04), SI (-0.01), CSA
(-0.71), CSMI (-0.02) and significantly positively associated with d2
(0.07), d3 (0.04), y (0.04), HAL (0.05). For males, age was significantly
negatively associated with d1 (-0.03), CSA (-0.36) and significantly
positively associated with d2 (0.04), d3 (0.05), y (0.03) and HAL (0.08).
A significantly stronger association between femoral neck fracture
sustainment and increasing age was found for the female cohort (OR
1.06 (95% CI 1.05, 1.07)), compared to the male (OR 1.02 (95% CI
1.01, 1.04)).
Conclusions: Increasing age is associated with an expansion (d3, y)
and lengthening (d2, HAL) of the femoral neck, which is associated
with decreased strength (SI, CSMI) in females only.
Apart from reduced CSMI in females only, age-related changes of
the shape of the proximal femur are similar between females and
males. Studies have shown CSMI to be one of the best predictors of
fracture risk beyond bone mineral density, therefore it may be that
reduction of CSMI in females only is partially responsible for the sexrelated differences of age-related femoral neck fracture risk.
Disclosure statement: All authors have declared no conflicts of
interest.
POSTER VIEWING II
POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
propose that such a proactive approach to reviewing radiograph
reports is likely to be more reliable in detecting VF patients, compared
with waiting to receive notification from The Radiology Department.
For the best use of limited resources,we have decided to restrict the
service to patients with vertebral fractures only.
Disclosure statement: All authors have declared no conflicts of
interest.
140. THE ASSOCIATION BETWEEN BREAST CANCER,
AROMATASE INHIBITION THERAPY AND OSTEOPOROSIS
Rebecca N. Andrews1,2, Alexander G. Oldroyd1,2, Bronwen Evans2,
Cathi Greenbank2 and Marwan Bukhari2,3
1
School of Health and Medicine, Lancaster University, Lancaster,
United Kingdom; 2Rheumatology, Royal Lancaster Infirmary,
Lancaster, United Kingdom; 3School of Clinical Sciences, University
of Liverpool, Liverpool, United Kingdom
TABLE 1 Baseline variables of each group
Mean age/years (SD)
Mean BMI/kg/m2 (SD)
Mean social deprivation
score (SD)
Number osteoporotic (%)
Breast cancer
n ¼ 509
Breast cancer
and aromatase
inhibitor n ¼ 352
Controls
n ¼ 4755
65.90 (9.80)
27.26 (5.13)
16.51 (12.23)
66.30 (9.53)
27.61 (5.14)
16.65 (12.51)
58.90 (11.71)
26.61 (5.14)
16.89 (13.02)
212 (41.65)
126 (35.87)
403 (8.46)
Disclosure statement: All authors have declared no conflicts of
interest.
141. LATERAL DXA SCANNING FOR VERTEBRAL
FRACTURE ASSESSMENT IS MORE USEFUL IN
POPULATION-BASED SETTINGS THAN AS PART OF
FRACTURE LIAISON SERVICES
Emma M. Clark1, Virginia C. Gould1, Louise Carter2, Leigh Morrison1
and Jon H. Tobias1
1
Academic Rheumatology, University of Bristol, Bristol,
United Kingdom; 2Rheumatology, North Bristol NHS Trust, Bristol,
United Kingdom
Background: Traditionally people are treated for osteoporosis if they
have a DXA result showing bone density T score <-2.5. If they are
within the osteopaenic range then the addition of other risk factors can
mean that treatment is recommended at this higher bone density (T
score >-2.5). The presence of a VF (approximately 12% of women
aged 50-79 have at least one vertebral deformity) indicates someone
at high-risk of future fractures, and they should be treated with antiosteoporosis medications if their bone density is osteopaenic.
However, less than one-third of women with VF are identified and
managed appropriately. The standard diagnostic test for identification
of VFs is a thoraco-lumbar radiograph which has a high radiation
exposure. Lateral DXA scanning for VFA has recently been developed
as an inexpensive, quick and lower radiation technique and is
potentially useful in screening patients for VFs, but the context in
which this is best used is currently unclear. In this study, we applied
our recent findings of a screening programme for VFs in older women
from Primary Care, by evaluating the use of this screening tool to
select patients for referral for VFA as part of a novel screening strategy
in primary care. In particular we aimed to determine whether VFA
screening is more efficient when applied to such a primary-care based
strategy, as compared with the context of patients referred for DXA
scans after low trauma fracture as part of FLS.
Methods: Two cohorts of women were recruited in parallel: Group 1
were identified from our primary care-based screening study as being
at high risk of VFs; Group 2 were identified from the NHS fracture clinic
(FLS) with a recent non-VF. The screening tool for Group 1 was the
published COSHIBA tool. The intervention was DXA with VFA.
Outcome was the impact of VFA results on putative treatment
decisions. This was assessed by comparing the proportion of patients
identified with VF with osteopenia who would otherwise not be
treated in the 2 groups. Ethics approval was obtained from the
Gloucestershire REC (07/Q2005/47).
Results: 251 women in Group 1 and 377 in Group 2 took part in this
study. Women in Group 1 (high-risk from primary care) were older and
had lower BMD than Group 2 from FLS. In Group 1, VFA identified 15
women with VF, of whom only 6 had osteoporosis on DXA, so the
results of VFA would change management in 9/251 (3.6%). In Group 2,
VFA identified 10 women with VF, of whom 5 had osteoporosis on
DXA. Results of VFA performed in FLS would change management in
5/377 (1.3%).
Conclusions: There may be a role in using VFA in a population-based
setting after screening for risk of VF. There is little justification for using
VFA as a routine part of FLS as it would only change management in
1% of cases. VFA is only likely to be cost-effective if it is used in a
targeted way in high-risk groups.
Disclosure statement: All authors have declared no conflicts of
interest.
142. ACTIVE VITAMIN D (1,25-DIHYDROXYVITAMIN D)
AND BONE HEALTH IN MIDDLE AGED AND ELDERLY MEN:
RESULTS FROM THE EUROPEAN MALE AGEING STUDY
Stephen R. Pye1, Dirk Vanderschueren2,3, Terence W. O’Neill1, David
M. Lee1, Ivo Jans3, Jaak Billen3, Evelien Gielen4, Michael Laurent4,5,
Frank Claessens5, Judith E. Adams6, Kate A. Ward7, Gyorgy Bartfai8,
Felipe Casanueva9, Joseph D. Finn10, Gianni Forti11,
Aleksander Giwercman12, Thang S. Han13, Ilpo Huhtaniemi14,
Krzysztof Kula15, Michael E. Lean16, Neil Pendleton17,
Margus Punab18, Frederick C. Wu10 and Steven Boonen4
1
Arthritis Research UK Epidemiology Unit, The University of
Manchester, Manchester, United Kingdom; 2Department of
Andrology and Endocrinology, Katholieke Universiteit Leuven,
Leuven, Belgium; 3Department of Laboratory Medicine, Katholieke
Universiteit Leuven, Leuven, Belgium; 4Leuven University Division of
Geriatric Medicine and Centre for Metabolic Bone Diseases,
Katholieke Universiteit Leuven, Leuven, Belgium; 5Department of
Molecular Cell Biology, Katholieke Universiteit Leuven, Leuven,
Belgium; 6Clinical Radiology, Imaging Science and Biomedical
Engineering, The University of Manchester, Manchester,
United Kingdom; 7MRC Human Nutrition Research, Elsie Widdowson
Laboratory, Cambridge, United Kingdom; 8Department of Obstetrics,
Gynaecology and Andrology, Albert Szent-Gyorgy Medical
University, Szeged, Hungary; 9Department of Medicine, Santiago de
Compostela University, Santiago de Compostela, Spain; 10Andrology
Research Unit, The University of Manchester, Manchester,
United Kingdom; 11Department of Clinical Physiopathology,
University of Florence, Florence, Italy; 12Department of Urology,
University of Lund, Malmo, Sweden; 13Department of Endocrinology,
Royal Free and University College Hospital Medical School, London,
United Kingdom; 14Department of Surgery and Cancer, Imperial
College London, London, United Kingdom; 15Department of
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: A number of studies have identified the increased risk of
osteoporosis in individuals with breast cancer. It is not clear whether or
not this association is due to the effects of breast cancer itself, or
aromatase inhibitor therapy. Breast cancer itself can cause decreased
bone mineral density (BMD) and its treatment, aromatase inhibition,
can cause decreased BMD too, through preventing the protective
function of oestrogen. This study aims to examine the changes in BMD
in patients with breast cancer and determine whether there is an
added association between aromatase inhibition and BMD loss.
Methods: Data of female individuals that underwent a Dual-energy Xray Absorptiometry scan at A DGH between 1992 and 2010 were
collated. The following data were collated: age, sex, body mass index
(BMI), social deprivation score, osteoporosis status (t-score < 2.5),
previous diagnosis of breast cancer, previous use of aromatase
inhibitor treatment. A female only control group with no identifiable risk
factors for osteoporosis was used as a comparator group. Logistic
regression modelling, adjusted for age, BMI and social deprivation
score, was used to examine any differences between the following
groups: previous breast cancer without aromatase inhibitor treatment,
previous breast cancer with aromatase inhibitor treatment; both case
groups were compared to each other, case groups were compared
against controls.
Results: Baseline characteristics of each group are outlined in Table 1.
212 (41.65%) of the breast cancer only group, 126 (35.87%) of the
aromatase inhibitor group and 403 (8.46%) of the control group were
osteoporotic. Compared to controls, the odds ratio of having
osteoporosis, after adjusting for age, BMI and social deprivation
score, was 6.21 (95% CI 5.02, 7.72) for present breast cancer and 4.63
(95% CI 3.59, 5.99) for breast cancer treated with aromatase inhibitors.
Comparing untreated breast cancer against treatment with aromatase
inhibitors gave an odds ratio of osteoporosis of 1.79 (95% CI 1.22,
2.65).
Conclusions: Individuals with breast cancer that have not received
aromatase inhibition appear to be at a higher risk of osteoporosis,
compared to controls and those that have received aromatase
inhibitors. These results indicate that breast cancer is significantly
detrimental to BMD, irrespective of treatment with aromatase
inhibitors. Further research is required to quantify the relationships
between breast cancer, its treatment and BMD.
iii103
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Wednesday 2 May 2012, 10.45 – 11.45
Andrology and Reproductive Endocrinology, Medical University of
Lodz, Lodz, Poland; 16Department of Human Nutrition, University of
Glasgow, Glasgow, United Kingdom; 17School of Community Based
Medicine, The University of Manchester, Manchester,
United Kingdom; 18Andrology Unit, United Laboratories of Tartu
University Clinics, Tartu, Estonia
143. MANAGEMENT OF GLUCOCORTICOID INDUCED
OSTEOPOROSIS
Cecilia Mercieca1, Jackie Webb2, Jacqueline Shipley2 and
Ashok Bhalla2
1
Academic Rheumatology Unit, Bristol Royal Infirmary, Bristol,
United Kingdom; 2Rheumatology, Royal National Hospital for
Rheumatic Diseases, Bath, United Kingdom
Background: Glucocorticoid induced osteoporosis (GIOP) is the most
common cause of secondary osteoporosis. In the UK up to 0.9% of
the general adult population is on glucocorticoids (GCs) at any point.
Osteoporotic fractures are associated with significant disability & pain.
The Royal College of Physicians have issued guidelines for management of GIOP in 2002 based on systematic review & evidence grading.
Since then more data on fracture risk and new therapies have
emerged. Recently the American College of Rheumatology guidelines
for GIOP have been published and mainly stratify risk and need for
treatment based on the FRAX tool. The aim of this audit was to
measure current practice in management of GIOP against RCP
guidelines and compare performance of RCP and the new ACR
guidelines for GIOP.
Methods: 115 (F 77, M 38) consecutive patients on GCs referred for
DEXA scan over a 1 year period were included.
Results: The mean age was 60.3 years (SD 15). 51 patients were over
65 years of age while 21 were premenopausal woman or males under
the age of 50 years. Patients were referred via direct access (54),
general rheumatology clinic (24) and osteoporosis clinic (37). The most
common reason for GC use was PMR (28) followed by respiratory
conditions (22) and inflammatory bowel disease (10). 23 had previous
fragility fracture. Half of the patients were recommended a follow up
scan, the mean follow up time was 2 years (SD 0.7).
In our cohort treatment was recommended in 73 patients following
RCP guidelines and in 69 patients following the ACR guidelines. For
those over the age of 65 years applying the ACR guidelines would
result in treatment of 43 out of 51 patients. In postmenopausal women
and males older than 50 years but younger than 65 years, treatment
was recommended in 22 cases by the RCP guidelines and in 26 cases
by the ACR guidelines.
Conclusions: For the over 65 years group the ACR GIOP guidelines
recommend treatment in a smaller number of cases particularly in
those whose FRAX score shows a low fracture risk compared to the
RCP guidelines.
There was not much difference in treatment recommendations
between the 2 guidelines for patients at medium or high risk of
fracture. A bone density scan in these patients did not influence
management.
In patients older than 65 years with a low risk for fragility fracture a
bone density scan may improve risk assessment and management.
Disclosure statement: All authors have declared no conflicts of
interest.
144. IS THERE AN ASSOCIATION BETWEEN ADOLESCENT
FEMALES’ SKIN TONE AND BEHAVIOUR WITH RESPECT
TO SUN EXPOSURE?
Sue Fairbanks1, Katie E. Moss2, Catherine Collins3 and
Philip Sedgwick4
1
Undergraduate, St George’s Hospital, University of London,
London, United Kingdom; 2Rheumatology, St George’s Hospital,
University of London, London, United Kingdom; 3Dietetics, St
George’s Hospital, University of London, London, United Kingdom;
4
Education, St George’s Hospital, University of London, London,
United Kingdom
Background: Vitamin D deficiency is associated with metabolic bone
disease. Most of the body’s vitamin D is produced in the skin following
exposure to ultraviolet B waves. Levels of the skin’s melanin content
dictate the necessary exposure time for sufficient UVB absorption
with darker skin requiring longer periods. Deficiency was found to be
more severe in non-white girls. This research aimed to discover the
behaviours behind the attitudes that influence teenage girls’ exposure
to sunlight.
Methods: In September 2011, using cluster sampling, a questionnaire
was completed by 330 female students, from a cohort of 360 students,
from two inner-city multi-ethnic schools, in Wandsworth, London. The
age range was16 to 18 years. Skin tone was self-selected. Attitudes
and behaviours around exposure, with reference to the summer of
2011, were determined. Intake of dietary sources, supplementation
and physical effects of deficiency were assessed in order to ascertain
the respondent’s vitamin D status. 7 respondents did not clarify skin
colour but are counted in the total of 330 participants.
Results: Within the groups, students not liking having a tan were as
follows; 77% of the ‘Dark’, 75% of the ‘Medium’, 31% of the ‘Olive’
and 31% of the ‘Pale’.
Participants who cited that they covered their body was 74% of the
‘Dark’, 76% of the ‘Medium’, 56% of the ‘Olive’ and 47% of the ‘Pale’
categories.
Reasons given for covering the body, within group analysis:
‘Religious’; ‘Dark’ 14 (26%), ‘Medium’ 57 (44%) and ‘Olive’ 20
(33%) and’Pale’ 4 (5%).
‘Cultural reasons’; ‘Dark’ 20 (15%), ‘Medium’ 20 (15%), ‘Olive’ 5
(8%) and ‘Pale’ 5 (6%).
However, the ‘Pale’ group 18 (23%) cited ‘Unwanted Darkening’ as
the most pertinent reason compared with ‘Dark’ 11 (20%), ‘Medium’
20 (15%) and ‘Olive’ 7 (11%) skin tones.
The statistically significant difference arose because the ‘Pale’ and
‘Olive’ skin tones were more likely to sunbathe, 1 to 3 times per week,
when compared with ‘Medium’ and ‘Dark’ skin tones, whilst the latter
two were most likely never to sunbathe.
Conclusions: In our study population, the reasons for avoiding the sun
varied with skin tone. There is a statistically significant difference in sun
exposure behaviour, as revealed by the Fisher test, showing that the
high risk groups most likely do not achieve adequate exposure.
TABLE 1 Time spent sunbathing summer 2011
Never
1-3 times week
Most days
Total
Pale (%)
Olive (%)
Medium (%)
Dark (%)
Total (%)
42 53.8
32 41.0
4 5.1
78 100.0
40 67.8
18 30.5
1 1.7
59 100.0
117 92.1
10 7.9
0 .0
127 100.0
49 90.7
5 9.3
0 .0
54 100.0
248 78.0
65 20.4
5 1.6
318 100.0
n (%). ‘Dr Philip Sedgwick, 2011’ Count, % within skin tone. Fisher’s Exact Test
used to test the hypothesis. Fisher’s test statistic ¼ 49.58; P < 0.0001.
Disclosure statement: All authors have declared no conflicts of
interest.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: 1,25-dihydroxyvitamin D (1,25(OH)2D) is the active
metabolite of vitamin D, however, little is known about its influence
on bone health. The aim of this study was to determine the influence of
1,25(OH)2D on bone health in middle-aged and older European men.
Methods: Men aged 40-79 years were recruited from population
registers in eight European centres for participation in a prospective
study of ageing: the European Male Ageing Study (EMAS). Subjects
completed lifestyle and health questionnaires and were invited to
attend for quantitative ultrasound (QUS) of the heel, assessment of
height and weight, and a fasting blood sample. Dual energy x-ray
absorptiometry (DXA) of the hip and lumbar spine was performed in
two centres. 1,25(OH)2D was measured using liquid chromatography
tandem mass spectrometry and 25(OH)D using radioimmunoassay.
Parathyroid hormone (PTH) and the bone markers, serum N-terminal
propeptide of type 1 procollagen (P1NP) and cross-links (b-cTX) were
also measured. Associations between the bone and vitamin D
parameters (all expressed as per standard deviation) were assessed
using linear regression, with the bone parameters as the dependent
variable and results expressed as b coefficients and 95% confidence
intervals (95%CI).
Results: 2783 men, mean age 60.0 years (SD ¼ 11.0) were included in
the analysis. Mean 1,25(OH)2D was 59.3 pg/ml and mean 25(OH)D was
24.4 ng/ml. After adjustment for age and centre, 1,25(OH)2D was
positively associated with 25(OH)D (b per SD ¼ 0.402; 95%CI 0.368,
0.437) though not with PTH (b per SD ¼ -0.034; 95%CI 0.070, 0.003).
After adjustment for age, centre, height, weight, lifestyle factors and
season of measurement, 1,25(OH)2D was negatively associated with
QUS (speed of sound) & DXA BMDa at the lumbar spine (b ¼ -0.077;
95%CI 0.116, 0.038 and b ¼ -0.111; 95%CI 0.209, 0.013
respectively) and positively associated with b-cTX (b ¼ 0.162; 95%CI
0.124, 0.201). 1,25(OH)2D was not associated with P1NP (b ¼ 0.017;
95%CI 0.025, 0.058). 25(OH)D was positively associated with QUS &
DXA parameters, but not related to either bone turnover marker.
Conclusions: In this population sample of European men, serum
1,25(OH)2D was associated with increased bone turnover and reduced
bone mass.
Disclosure statement: All authors have declared no conflicts of
interest.
POSTER VIEWING II
POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
145. NHS RADIOGRAPH REPORTS OF VERTEBRAL
FRACTURE COMPARE FAVOURABLY WITH FORMAL
STANDARDIZED REPORTING METHODS, BUT SOME
NHS REPORTS ARE UNCLEAR
Emma M. Clark1, Virginia C. Gould1, Leigh Morrison1 and
Jon H. Tobias1
1
University of Bristol, Bristol, United Kingdom
TABLE 1.
NHS report
ABQ n (%)
No VF (n ¼ 230)
Possible VF (n ¼ 52)
Definite VF (n ¼ 28)
VF no yes
VF no yes
VF no yes
QM n (%)
226 (98.3) 4 (1.7)
41 (78.9) 11 (21.2)
5 (17.9) 23 (82.1)
VF no yes
VF no yes
VF no yes
214 (93.0) 16 (7.0)
38 (73.1) 14 (26.9)
8 (28.6) 20 (71.4)
Disclosure statement: All authors have declared no conflicts of
interest.
146. INFLUENCE OF ANTI-EPILEPTIC DRUGS ON
BONE MINERAL DENSITY
Joshua Parker1, Cathy Greenbank1, Bronwen Evans1,
Alexander G. Oldroyd1 and Marwan Bukhari1
1
Rheumatology, Royal Lancaster Infirmary, Lancaster,
United Kingdom
Background: It has been documented since the 1960s that
antiepileptic drugs (AED) have a negative impact on bone mineral
density (BMD) which of course has implications for osteoporosis and
fracture risk 1, 2. There are many possible mechanisms for this;
however the main underlying pathology seems to be increased bone
turnover 3. Nevertheless it is not known if bone can recover after
stopping AED therapy.
Objectives:
This study aims to analyse the relationship between AEDs and
BMD, seeking to discover if cessation of therapy impacts BMD using a
case controlled approach.
Methods: Patients attended a district general hospital between 1994
and 2010 to undergo bone density dual x-ray absorptiometry. BMD in
the lumbar vertebrae (L1-4) and femoral neck was recorded as well as
clinical risk of osteoporosis, AED use and indications for scanning.
From these, 3 groups were identified: a group currently taking AEDs, a
group that had previously taken AEDs and the 3rd group, an age and
sex matched control group. Comparison of these groups was made
using Student’s T Test for continuous variables and a Chi Squared test
for categorical variables.A logistic model was fitted to examine the
BMD difference between current and previous AED use in the hip and
spine.
Results: 346 patients were taking anticonvulsants at the time of
scanning, 76% (263) were female with an average age of 59.4 years
old (SD 12.8). 84% (72) of the 86 patients previously taking
anticonvulsants were female with an average age of 57.1 years old
(SD 13.4) which was the same as the control group. The average
number of indications for scanning in the previous anticonvulsant
group was significantly lower than in the current AED group
(p < 0.026).
Base changes in BMD and percentage of patients with osteoporosis are shown in table 1 below, significant differences are noted in Key:
The logistic model showed that the odds of a lower BMD was 0.82
(95%CI 0.25,2.75) in the spine and 0.16 (95% 0.03, 0.88) in the hip.
Conclusions: Comparison has shown that BMD does improve with
cessation of AED therapy but not completely. Patients who have
previously taken AEDs have a significantly lower BMD than those still
on therapy, but not as low as controls. Of note, femoral neck BMD is
significantly decreased in previous AED patients compared to controls
which is an indicator of fracture risk in osteoporosis. Unfortunately it
was outside the scope of this project to look at specific AEDs, length of
AED treatment or how long patients no longer taking AEDs had spent
off treatment.
TABLE 1.
BMD lumbar spine (L1-4)
Femoral neck mean BMD
Osteoporosis (%)
Previous fracture (%)
Controls
PAED
Previous AED
therapy (PAED)
Currently taking
AED therapy
(CAED)
1.05
0.84
44.8
0
1.07
0.89*,**
43.02
27.91*,**
1.06
0.084
45.95
40.46
*Significant difference between PAED and CAED (p < 0.05); **Significant difference
between PAED and controls (p < 0.05)
Disclosure statement: M.B. has attended meetings at Pfizer, Roche,
Abbott, UCB and Menarini, sat on advisory boards of Pfizer, Roche,
Abbott and UCB, and received honoraria from Pfizer, Roche, Abbott,
UCB and Menarini. All other authors have declared no conflicts of
interest.
147. FETAL AND INFANT GROWTH PREDICT HIP
GEOMETRY AT SIX YEARS OLD: FINDINGS FROM
THE SOUTHAMPTON WOMEN’S SURVEY
Nicholas C. Harvey1, Zoe A. Cole1, Sarah R. Crozier1,
Georgia Ntani1, Pam A. Mahon1, Sian M. Robinson1,
Hazel M. Inskip1, Keith M. Godfrey1,2, Elaine M. Dennison1 and
Cyrus Cooper1
1
MRC Lifecourse Epidemiology Unit, University of Southampton,
Southampton, United Kingdom; 2Southampton NIHR Nutrition,
Diet and Lifestyle Biomedical Research Unit, University of
Southampton, Southampton, United Kingdom
Background: We have previously demonstrated that poor early
growth predicts risk of hip fracture in older adulthood, and that this
association might be mediated through altered proximal femoral
geometry. It is not clear which growth period might be of particular
importance, and whether changes in hip structure might already be
present in childhood. We therefore aimed to investigate the relationships between early growth trajectory and proximal femoral geometry
at six years old in a prospective population-based cohort, the
Southampton Women’s Survey (SWS).
Methods: 493 mother-offspring pairs were recruited from the SWS.
Fetal linear size at 11 weeks (crown-rump length) and at 19 and 34
weeks (femur length) was assessed using high resolution ultrasound;
postnatal linear growth (length or height) was measured at birth, 6, 12,
24, 36 and 48 months. Within group Z-scores were created, adjusting
for gestation, and conditional regression modelling yielded mutually
independent growth variables for each time period. Proximal femoral
size, density and geometry at 6 years were assessed using DXA
(Hologic Discovery, Hologic Inc., Bedford, MA, USA) and hip structure
analysis software.
Results: After adjustment for child’s age, sex and milk intake, linear
growth at all fetal and infant time intervals was positively related to
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: Vertebral fractures (VFs) are common: approximately
12% of older women have at least one vertebral deformity, the majority
of which will be osteoporotic in origin, but less than a third come to
clinical attention. We have recently reported on the results of a large
RCT of a trial of a screening programme aiming to identify older
women with osteoporotic VFs by using a predefined set of clinical
triggers. The results were encouraging as allocation to screening
approximately doubled prescribing of medication for osteoporosis
(OR for new prescriptions of 2.24, 95%CI 1.16 to 4.33). However,
despite this increase, less than half of women with a VF had received a
new prescription for anti-osteoporosis medications within 12 months.
Reasons for this may include lack of awareness of importance of
VFs in primary care, as well as individual patient characteristics such
as cognitive impairment. However, the main reason may be the nonstandardized nature of NHS radiograph reporting. We therefore
undertook an in-depth analysis of the radiology reports produced as
part of our RCT with an aim of identifying areas for improvement.
Methods: This study consisted of 310 spinal radiographs performed
on older women, all of whom had been identified as being at high
risk for VF as part of a previous study (COSHIBA). The radiographs
were interpreted using three methods: standard NHS reporting; the
algorithm-based qualitative (ABQ) approach; and quantitative morphometry (QM) by SpineAnalyzer software, with presence of VF being
defined as 25o height reduction. The standard NHS reporting was
carried out by the on-duty reporting radiologist for that day, and could
have been one of approximately 40 radiologists. The ABQ and QM
were carried out by a researcher (EC) several weeks apart in an
anonymized manner without knowledge of the NHS report, result of
QM or ABQ.
Results: NHS reports were categorized into 230 (74.2%) without VF
and 28 (9.0%) with definite VF. There were a further 52 (16.8%) where
the reports were unclear (using words such as ‘collapse’ instead of
fracture, or use of ‘probably’). Analysis by ABQ and QM showed the
NHS reports had good agreement for no VF and definite VF. But the
‘possible VF’ category contained approximately 70-80% without
actual osteoporotic VF.
Conclusions: Standard NHS spinal radiograph reports of VF compare
favourably with ABQ and QM methods. However, approximately a fifth
of reports were unclear. Clarifying this group and re-categorizing into
definite or no VF is needed to improve communication to GPs, and
allow appropriate treatment with anti-osteoporosis medications for
this group of women at very high risk for future fractures.
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Wednesday 2 May 2012, 10.45 – 11.45
total hip bone area and bone mineral content, and to femoral neck
cross-sectional area and cross-sectional moment of inertia (CSMI).
The strongest associations were with growth in late gestation (19-34
week linear growth and CSMI at 6 years: beta ¼ 0.26 cm4/sd,
p < 0.0001 versus 11-19 week linear growth and CSMI: beta ¼ 0.11
cm4/sd, p ¼ 0.06), and in the first two years of postnatal life (0-1 year
linear growth and CSMI: beta ¼ 0.28 cm4/sd, p < 0.0001; 1-2 years:
beta ¼ 0.34 cm4/sd, p < 0.0001), with progressively weaker relationships over years 3 (beta ¼ 0.23 cm4/sd, p ¼ 0.0001) and 4 (beta ¼ 0.11
cm4/sd, p ¼ 0.14). Associations were similar in when boys and girls
were analysed separately.
Conclusions: We have demonstrated that early growth predicts
proximal femoral size, mineralization, geometry and strength at six
years old. The relationships are particularly strong in late pregnancy
and in the first two years of postnatal life suggesting that these might
be critical periods in which there is capacity for long term influence on
the later skeletal growth trajectory.
Disclosure statement: All authors have declared no conflicts of
interest.
Matthew Bridges1 and Sheila Ruddick1
1
Rheumatology, Darlington Memorial Hospital, Darlington,
United Kingdom
Background: The World Health Organization Fracture Risk
Assessment Tool (FRAX½) enables a patient’s ten year probability of
hip fracture, and major fracture (hip, wrist, humerus, and clinical
vertebral) to be calculated, and is expressed in percentage terms.
Guidelines written by the National Osteoporosis Guideline Group
(NOGG) can then be used (in the absence of bone densitometry) to
classify patients into one of three groups; 1) Those requiring treatment,
2) those requiring axial bone density measurement, and 3) those
requiring reassurance only. For FRAX/NOGG to be of most value, it
needs to be able to reliably identify those patients who will sustain a
fracture, so appropriate investigation / treatment can be instituted.
Methods: We retrospectively analysed data on 300 post-menopausal
women who had attended our hospital fracture clinic after sustaining a
low trauma wrist fracture, in order to calculate the proportion of these
patients that NOGG would have deemed appropriate for bone
densitometry measurement or treatment with bone sparing therapy,
prior to sustaining their fracture. Patients who were already on bone
sparing therapy, or who were < 40 years or >90 years of age, were
excluded. Post-menopausal women who had sustained fractures prior
to the incident fracture were also excluded, since NOGG guidelines
recommend that these patients can be treated with bone sparing
agents without the need for FRAX assessment.
Results: The patients had a mean age (standard deviation) of 68.0 (9.9)
years. 194 (74.4%) patients had no risk factors for fracture. We then
calculated the NOGG classification for each patient excluding the
incident fracture. 4 patients (1.3 %) were classified in the ‘‘treat’’
group, 64 (21.3%) in the ‘‘measure BMD’’ group, and 232 (77.1%) in
the ‘‘reassure’’ group. NOGG guidelines advocate the use of the FRAX
tool only in those patients who have risk factors for fracture. Of the 106
patients who did have risk factors, NOGG would have recommended
‘‘treat’’ in 4 (3.7%) patients, ‘‘measure BMD’’ in 36 (33.6%), and
‘‘reassure’’ in 30 (62.6%).
Conclusions: Our data shows that the majority of women would have
been identified by the NOGG guideline as requiring reassurance and
lifestyle advice only, immediately prior to sustaining a wrist fracture.
We would therefore guard against an over reliance on FRAX/NOGG in
deciding which patients with risk factors for fracture to investigate or
treat.
Disclosure statement: All authors have declared no conflicts of
interest.
149. PLACENTAL SIZE PREDICTS OFFSPRING BONE MASS:
FINDINGS FROM THE SOUTHAMPTON WOMEN’S SURVEY
Christopher R. Holroyd1, Pam Mahon1, Sarah R. Crozier1,
Keith Godfrey1, Hazel M. Inskip1, Cyrus Cooper1,2 and
Nicholas C. Harvey1
1
MRC Lifecourse Epidemiology Unit, University of Southampton,
Southampton, United Kingdom; 2NIHR Musculoskeletal Biomedical
Research Unit, Institute of Musculoskeletal Sciences, University of
Oxford, Oxford, United Kingdom
Background: Osteoporosis is a major cause of morbidity and mortality
through its association with age-related fractures. Early environmental
influences, such a maternal smoking and physical activity can
influence offspring bone mineral accrual. These associations may be
mediated by placental size or function. In this study we investigate the
relationship between placental size and offspring bone mass using the
Southampton Women’s Survey (SWS).
Methods: The SWS is a unique prospective cohort of 12,583 nonpregnant women aged 20-34 years, of which 3,156 subsequent
singleton pregnancies were followed. Detailed placental measurements were obtained by fetal high resolution ultrasound scanning at 19
weeks. In a subset of offspring, neonatal whole body bone area (BA),
bone mineral content (BMC), areal bone mineral density (aBMD) and
body composition (total and percentage fat and lean) were measured
by DXA with specific paediatric software (Lunar DPX-L) within the first
two weeks of birth. Pearson correlation and linear regression were
used to relate placental measurements to neonatal body composition
and bone mass.
Results: We identified 757 mother-neonate pairs with complete
ultrasound and DXA data. The statistically significant, positive
predictors of BA, BMC and aBMD (p < 0.05) included placental
circumference, length of attachment to the uterine wall, crosssectional area and volume. Additionally, there was a significant
positive association between placental volume and total lean mass,
total fat mass and percent fat, but a negative association with percent
lean (p < 0.05). Thus, as placental size increased, overall nonatal size
increased with an increase in percent fat and a reduction in percent
lean mass. These associations remained after adjusting for maternal
factors known to affect offspring bone mass.
Conclusions: Placental size is positively associated with intrauterine
bone mineral accrual. These associations appear independent of
maternal factors known to influence neonatal bone mass, suggesting
that these factors might act through modulation of placental function
rather than placental size. Low placental volume early in pregnancy
may be a marker of a smaller postnatal skeletal envelope and
potentially increased risk of fracture in older age.
Disclosure statement: All authors have declared no conflicts of
interest.
150. MODIFYING FRAX/NOGG GUIDELINES IN
RHEUMATOLOGY PATIENTS RECIEVING
CORTICOSTEROIDS: DOES IT MAKE ANY DIFFERENCE?
Matthew Bridges1 and Sheila Ruddick1
1
Rheumatology, Darlington Memorial Hospital, Darlington,
United Kingdom
Background: The current FRAX algorithm incorporates use of
corticosteroids as a dichotomous risk factor (yes/no). However,
guidance for the adjustment of FRAX estimates based upon the
dose of corticosteroids have been developed, which increase the
estimated risk of fracture in patients taking > 7.5 mg prednisolone per
day, and reduce it in patients receiving < 2.5 mg daily. We applied both
the standard FRAX / NOGG guideline, and NOGG guidelines based on
FRAX scores adjusted for dose of corticosteroid, to a group of patients
receiving long term steroids, and analysed resulting differences in
NOGG recommendations.
Methods: We retrospectively analysed data on 77 consecutive
attendees of our rheumatology out-patient department who were
receiving prednisolone, at any stable dose for three months or more,
and applied NOGG guidelines (in the absence of bone density
assessment) to classify the patient into one of the three groups; 1)
those patients requiring treatment, 2) patients who require bone
density assessment, or 3) patients requiring reassurance only. Patients
were first classified using standard FRAX fracture estimates, and then
a second time using steroid-dose-adjusted FRAX fracture risk
estimates. The number of patients who were classified differently
between these two methods was calculated. Women who had
sustained a previous fracture were excluded, since NOGG guidance
suggests these patients can be treated with bone sparing therapy
without the need for bone density assessment.
Results: The 77 patients had a mean age (standard deviation) of 67.9
(8.6) years, and 63 (82%) were female. The patients had the following
rheumatic diseases; 51 rheumatoid arthritis (RA), 15 polymyalgia
rheumatica, 7 connective tissue disease, and 4 other conditions. Using
standard FRAX / NOGG guidelines, 46 patients were classified as
requiring bone density assessment, 17 were classified as requiring
reassurance only, and the remaining 14 patients were classified as
needing bone sparing therapy. 65 patients were taking between 2.5 7.5 mg prednisolone daily, so required no alteration in their FRAX /
NOGG classification. 1 patient was receiving < 2.5 mg daily, and 11
patients were receiving > 7.5 mg daily. Of these 12 patients, only 1 had
a change in NOGG classification when adjusted FRAX / NOGG was
used.
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148. FRAX/NOGG HAS LOW SENSITIVITY IN PREDICTING
WRIST FRACTURES IN POST-MENOPAUSAL WOMEN
POSTER VIEWING II
POSTER VIEWING II
Conclusions: Our data shows that the majority of our patients were
receiving doses of corticosteroids between 2.5 - 7.5 mg daily, and that
adjustment of FRAX estimated risk of fracture is therefore unnecessary
in these patients. Even in those patients taking corticosteroids outside
this dose range, few have their NOGG classification changed when the
FRAX estimate of fracture risk is adjusted for the dose of corticosteroid
used.
Disclosure statement: All authors have declared no conflicts of
interest.
151. TERIPARATIDE IN DAILY PRACTICE:
THE BELFAST EXPERIENCE
Thomas McNeilly1, Collette McNally1, Tim Beringer2 and
Michael Finch1
1
Musgrave Park Hospital, Belfast HSCT, Belfast, United Kingdom;
2
Royal Victoria Hospital, Belfast HSCT, Belfast, United Kingdom
PAEDIATRIC AND ADOLESCENT
RHEUMATOLOGY
152. PRE-FORMED ORTHOSES IN JUVENILE IDIOPATHIC
ARTHRITIS: RESULTS FROM AN RCT
Andrea Coda1, Joyce Davidson2, Jo Walsh2, Peter Fowlie3,
Tom Carline1 and Derek Santos1
1
Podiatry, Queen Margaret University, Edinburgh, United Kingdom;
2
Paediatric Rheumatology, Royal Hospital for Sick Children,
Edinburgh, United Kingdom; 3Paediatric Rheumatology, Ninewells
Hospital, Edinburgh, United Kingdom
iii107
Background: Currently there is limited evidence supporting podiatric
treatment of children with JIA. This research aimed to determine
whether pre-formed cost-effective orthoses impacted on pain, quality
of life (primary outcomes) and/or gait-parameters (secondary outcomes) in children affected by JIA. The RCT aims to strengthen and
add new knowledge to the podiatric management of children affected
by this paediatric condition.
Methods: The trial took place at the Gait Analysis laboratory at Queen
Margaret University - Edinburgh and at the TORT Centre, Ninewells
Hospital-Dundee. Children with JIA, as diagnosed by a consultant
paediatric rheumatologist, were block randomized. Intervention was
blinded to the patients. The trial group was supplied with Slimflex Plus
insoles, with the addition of chair side corrections and the control
insole received was made with leather board (1 mm thick) without
corrections. Both insoles had the same black EVA top cover. Primary
outcome measures were recorded at each of the 3 data recording
appointments over the 6 months period, using validated questionnaires such as VAS, CHAQ and PedsQL. Tekscan½ equipment (FScan½ and HR WalkwayÕ ) measured in-shoe pressure and force data
with and without orthotic intervention, using same type of sensors of
equal resolution. Multiple foot strikes and repetitive gait patterns were
compared pre and post-treatment.
Results: Sixty children were recruited; 48.3% (n ¼ 29) control and
51.7% (n ¼ 31) active treatment group. Within the control group 20.7%
(n ¼ 6) of patients were male. Within the active treatment group, 29%
(n ¼ 9) subjects were male. Age ranged between 5 to 18 years. In order
to attribute any effect solely on the FOs intervention, details of changes
of medication and/or new joint injections were recorded during the
trial. 65.5% (n ¼ 19) of the control group were on stable medications.
74.2% (n ¼ 23) of the children receiving active treatment were on
stable medication. Overall, 99.4% (n ¼ 179/180) appointments were
completed and contributed to this preliminary data analysis.
Significant improvement was identified in the primary outcomes
favouring active treatment with regards to pain and quality of life
measures: VAS (p < 0.05); PedsQL paediatric-generic (p < 0.05) Peds
paediatric rheumatology (p < 0.05); PedsQL parent generic (p < 0.05);
PedsQL parent rheumatology (p < 0.05). In all these quality of life tools,
clinical significance was also obtained. Significant differences were
also identified between the groups for gait time, stance time, total
plantar surface, heel contact, midfoot, 5th metatarsal head and distal
phalanx.
Conclusions: The results show that pre-formed orthoses are effective
in improving pain, quality of life and most gait parameters in JIA
children. This research also provides new evidence to the role of
podiatrists within the multidisciplinary team in paediatric rheumatology
and hopes to raise the profile of podiatrists working within the
paediatric hospitals and private practices.
Disclosure statement: All authors have declared no conflicts of
interest.
153. COMPARISON OF METHOTREXATE INDUCED NAUSEA
AND VOMITING BETWEEN ADOLESCENT AND ADULT
PATIENTS WITH INFLAMMATORY ARTHRITIS
Pravin Patil1, Christine Rawcliffe2, Abigail Olaleye2,
Samantha Moore2, Amy Fox2, Debajit Sen2 and Yiannis Ioannou2
1
Rheumatology, Southend University Hospital, Southend,
United Kingdom; 2Rheumatology, University College London
Hospital, London, United Kingdom
Background: Nausea is one of the most frequent side-effects of
methotrexate. However, there is very little literature available in
adolescents on its prevalence and to our knowledge there are no
published comparative studies between adolescents and adults.
We conducted a cross sectional study to determine the prevalence
of methotrexate induced nausea and vomiting in patients with juvenile
idiopathic arthritis (JIA) and compared it with adult patients with
inflammatory arthritis. We also looked at the factors associated with
methotrexate induced nausea and vomiting in an attempt to define
predictors.
Methods: Inflammatory arthritis patients treated with methotrexate
were identified in the adolescent rheumatology clinic and adult drug
monitoring clinic over a period of 6 weeks. A questionnaire was
constructed containing questions pertaining to the onset of nausea
and vomiting upon taking methotrexate, prior to (anticipatory) and
when thinking (associative) of methotrexate intake. On each item
patients could score intensity as mild, moderate or severe. Duration of
symptoms, folic acid supplementation and use of anti-emetics were
also recorded.
Results: 35 adults (60% females, mean age 54 SD 47.6) and
31 adolescent patients (74% females, mean age 16 SD16.8) were
surveyed. 74% of adolescent patients reported nausea and 45%
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Background: Teriparatide is a treatment option for osteoporosis in
post-menopausal women and osteoporotic male patients. As an
anabolic agent it stimulated new bone formation increasing bone mass
and is administered as a daily subcutaneous injection for a duration up
to 24 months. NICE has made specific recommendations for the use of
teriparatide as a second line therapy in post-menopausal patients.
Beyond clinical trials there is limited data regarding it’s use in daily
clinical practice. We performed an analysis of the use of teriparatide so
far within our trust
Methods: Prospectively, baseline data had been collated for patients
when commenced on teriparatide with further information collected at
4 and 18 months and stored in a local computer database. Analysis
was performed retrospectively with data being extracted from the
database in 2011.
Results: 138 patients (female-129, male-9) have been commenced on
teriparatide since 2007 within the Belfast HSCT. The average age at
commencement was 74 (range 46-90). Baseline data was recorded
regarding number of prior fractures and previous use of antiresorptive
therapy. At the time of analysis 60 patients had completed an 18
month course while 25 had stopped teriparatide prematurely and 53
patients were in the middle of the treatment course.
Bone mineral density (BMD) was measured at the start and end of
treatment. Average spinal BMD increased by 8.3% over 18 months (T
score average [-3.67] 0 months vs [-3.19] 18 months). Average femoral
neck BMD increased by 3.5% over 18 months (T score average [-2.83]
0 months vs [-2.78] 18 months)
Bone turnover markers P1NP and CTX were measured at 0, 4 and
18 months. Average P1NP at commencement was 35.7 ng/mL,
peaking at 117.3 ng/mL at 4 months and dropping to 81.5 ng/mL at
18 months. Average CTX at commencement was 0.316 pg/mL,
peaking at 0.597 pg/mL at 4 months and dropping to 0.451 pg/mL at
18 months.
EuroQoL5 and patient VAS demonstrated an improvement in
patient health status over the 18 months treatment course (EuroQol5
[0.404] 0 months vs [0.611]18 months, Patient VAS [51.9] 0 months vs
[64.3] 18 months).
Conclusions: This analysis of teriparatide usage within the Belfast
HSCT supports the clinical trial data published by Neer et al,
demonstrating a significant improvement in BMD over the course of
treatment with appropriate increases in bone turnover markers. The
change in EuroQoL5 and Patient VAS score highlight improvement in
health status with successful treatment. The significant number of
patients who did not complete the full treatment course illustrate the
practical realities of it’s use within daily clinical practice
Disclosure statement: All authors have declared no conflicts of
interest.
Wednesday 2 May 2012, 10.45 – 11.45
iii108
Wednesday 2 May 2012, 10.45 – 11.45
154. OSTEOSARCOMA CELL CULTURE ON COLLAGEN
SURFACES AND IN HYPOXIA ALTERS MMP EXPRESSION
Sohail Nisar1, Kenneth Rankin1 and Mark Birch1
University of Newcastle upon Tyne, Musculoskeletal Research
Group, Institute of Cellular Medicine, Newcastle upon Tyne,
United Kingdom
1
Background: Osteosarcoma is the most common primary malignant
bone tumour in children. The survival rate has not improved much over
the last 25 years, and therefore there is a lot to learn about the
pathogenesis of this cancer. The interactions of tumour cells with their
environment and hypoxia have been identified as key drivers of tumour
growth and metastasis. Matrix-metallo proteinases (MMPs) are
involved in this process. MMPs are zinc-endopeptidases that are
able to degrade the extra-cellular matrix and are over-expressed in
many tumours. Membrane-type (MT1)-MMP and MMP-2 expression is
positively associated with tumour progression in a range of tumours,
but their role is not well characterized in osteosarcoma.
Methods: Cells were cultured to 80% confluence on culture plastic or
collagen surfaces and then treated with 20% or 1% oxygen and serum
free or osteoblast conditioned media (contains excess proMMP-2).
At 48 hours cells were assessed using the following techniques:
Immunofluorescence - incubation with MT1-MMP antibody and
FITC secondary. Coverslips were mounted on slides with DAPI and
photographed.
Western Blot - cell lysates were probed for MT1-MMP.
Zymography - culture supernatants were assessed for gelatinase
expression.
Results: Proliferation was assessed using the SRB assay which
showed osteosarcoma cells proliferate slightly slower in hypoxia.
Immunofluorescence microscopy was employed to visualize MT1MMP - this revealed MT1-MMP packaging and localization was altered
in hypoxia and there was formation of invadopodia on collagen.
Gelatinase expression, assessed using zymography of supernatants,
demonstrated increased proMMP-2 activation by cells cultured on
collagen, particularly by U2OS cells. Cell lysates were probed for MT1MMP using western blotting. ELISA of the culture supernatant was
used to measure TIMP-2 expression. Less active MT1-MMP was
detected in the lysates of the U2OS cells which coincided with a
decreased amount of TIMP-2 detected in the supernatant.
Conclusions: This study contributes to our understanding of the
activation of MMPs and the possible role of MT1-MMP in this regard.
Disclosure statement: All authors have declared no conflicts of
interest.
155. PROTEOMIC PROFILING OF THE SYNOVIAL
MEMBRANE IN JUVENILE IDIOPATHIC ARTHRITIS
Sorcha Finnegan1, Madeleine Rooney1 and David S. Gibson1
1
Centre for Infection and Immunity, Queen’s University, Belfast,
Belfast, United Kingdom
Background: Juvenile idiopathic arthritis (JIA) is one of the most
common chronic childhood diseases with a prevalence of around
1/1000. Over time JIA can result in persistent joint inflammation
leading to chronic pain and stiffness, joint deformity and damage.
Disease aetiology remains unknown and investigation of disease
pathology at the level of the synovial membrane (SM) is required if
we want to begin to understand disease at the molecular and
biochemical level. Studies in this area are non-existent, mainly due
to ethical difficulties in acquiring samples from children. In our previous
immunohistochemical (IHC) study we found significant variation
between the IHC profiles of early, treatment-naı¨ve JIA SM in three
JIA subgroups (Finnegan et al., 2011). Thus we further undertook
proteomic analysis of these samples to identify protein expression
profiles that could define JIA subgroups and provide insight into
disease pathology.
Methods: SM biopsies were acquired from 16 treatment-naive, early
disease-stage patients (8 polyarticular and 8 persistent oligoarticular)
under general anaesthetic. Biopsies were immediately snap frozen and
stored at 808C. Protein was extracted from SM in DIGE lysis buffer.
Each SM sample was minimally labeled with either Cy5 or Cy3
fluorescent dyes and an internal pooled standard (Cy2) was included
on each gel. Proteins were separated by two-dimensional gel
electrophoresis. Gels were scanned using a Typhoon 9410 imager
(GE Healthcare, Bucks, U.K.) and gel images were analysed using
Progenesis Samespots software (Nonlinear Dynamics Ltd. Newcastle
upon Tyne, U.K.). Proteins displaying a 2-fold change or greater
between oligoarticular and polyarticular patients were identified by
mass spectrometry (MS) with expression further verified by Western
blotting. Proteins were then localized within the SM by IHC.
Results: 2D DIGE analysis of SM detected an average of 800 proteins
on each 2D gel. There was significant variation in protein expression
between oligoarticular and polyarticular patients. There were a number
of proteins that were unique to the polyarticular patients as well as
proteins that were unique to oligoarticular patients. Ongoing analysis
to localize these proteins in the SM is being undertaken. The data
indicates that synovial membrane proteome profiles could be used to
stratify patients based on disease subgroup.
Conclusions: Current proteomic platforms such as 2D DIGE and MS
provide the means to define disease through protein expression
analysis. They also provide an insight into the pathways involved in
disease. Ultimately this could help us better understand the pathogenic mechanisms underlying JIA. The ability to identify, quantify and
localize specific target proteins in our patient samples would not only
provide a novel insight into JIA disease pathology but may also provide
potential therapeutic targets.
Disclosure statement: All authors have declared no conflicts of
interest.
156. EXPLORING THE RELATIONSHIPS BETWEEN ADULT
JUVENILE IDIOPATHIC ARTHRITIS AND EMPLOYMENT
Ajay Malviya1, Calum M. Ferris2, Stephen P. Rushton3,
Helen E. Foster4, Helen Hanson4, Karthik Muthumayandi4 and
David J. Deehan4
1
Wansbeck General Hospital, Northumbria Healthcare NHS
Foundation Trust, Ashington, United Kingdom; 2Medical School,
Newcastle University, Newcastle upon Tyne, United Kingdom;
3
School of Biology, Newcastle University, Newcastle upon Tyne,
United Kingdom; 4Freeman Hospital, Newcastle upon Tyne Hospitals
NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
Background: The chronicity of symptoms of Juvenile Idiopathic
Arthritis (JIA) from childhood and attendant potential disability, despite
advances in medical therapies, may adversely influence educational
attainment and the ability to secure and maintain gainful employment.
We investigated the impact of patient and disease-specific factors on
education and employment outcomes in an adult JIA population.
Methods: A prospective, observational cohort study of 103 consecutive adult patients attending a JIA continuity clinic was performed.
These included questions on educational achievement and employment status; a Health Assessment Questionnaire (HAQ score); and, for
those who were in employment, a Work Instability Score (RA-WIS).
Structural equation modelling was used to explore the complex
interactions between JIA subtype, age, disease duration, functional
disability, educational achievement and employment outcomes including employment stability and job classification status.
Results: The median age of the patients was 24 years (range 17-71)
with median disease duration of 19 years (range 7-67). Of the 103
patients, 64% (n ¼ 66) were in either full- or part-time employment.
Functional disability (HAQ score) was significantly lower in patients
who were in employment (mean ¼ 0.83, s.d. ¼ 0.85,) compared to
those not in any (mean ¼ 1.25, s.d. ¼ 0.92) (p ¼ 0.03), and those with
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vomiting versus 20% and 6% respectively for adults patients
(p < 0.0001 nausea and p < 0.0001 vomiting). There was no significant
difference in the average dose of methotrexate in both groups.
Interestingly, patients on parenteral methotrexate reported higher
prevalence of nausea compared to those on oral methotrexate (87%
versus 63%, P < 0.0002). Those who suffered from nausea and
vomiting nearly all experienced these symptoms after methotrexate
intake and around 50% patients had associative nausea. While none of
the adult patient experienced anticipatory or associative vomiting,
21% of total adolescents surveyed reported these symptoms. Nausea
persisted more than 1 day in 48% of the adolescent patients.
Surprisingly, none of adult patient suffering these symptoms was
taking anti-emetic and only 22% of adolescents were on anti-emetics.
We identified that younger age, longer use of methotrexate; female
gender and parenteral administration of methotrexate were associated
with nausea and vomiting (p < 0.05 for all).
Conclusions: This study revealed a significantly higher prevalence;
severity and duration of methotrexate induced nausea in adolescents
and young adults as compared to adults. The frequent occurrence of
anticipatory and associative complaints in adolescents suggests that
psychological factors play an important role in methotrexate intolerance in teenagers. Folic acid dose was not associated with high
prevalence of nausea and vomiting. We identified that younger age,
longer use of methotrexate; female gender and parenteral administration of methotrexate were associated with nausea and vomiting.
Disclosure statement: All authors have declared no conflicts of
interest.
POSTER VIEWING II
POSTER VIEWING II
oligoarticular JIA (t ¼ 2.29, p ¼ 0.02) versus other JIA subtypes.
Educational achievement was not influenced by JIA subtype
(F ¼ 1.18, p ¼ 0.33). Educational achievement at GCSE (F ¼ 11.63
p ¼ 0.001) had a positive impact on the type of job achieved in later life,
with higher success leading to more professional or managerial posts.
Job stability was influenced positively by educational achievement at
GCSE and negatively by the disability score (t ¼ 10.94 p ¼ 6.36-16),
which were themselves impacted by age of patient.
Conclusions: The impacts of JIA on subsequent employment are not
well-defined. This is the first study to formally model key patient and
disease variables for employment in adult patients with JIA. Previous
work has highlighted higher unemployment rates within this patient
group. Our results suggest that there is an interaction between
disability, education and employment that is more subtle: influencing
both job classification status achieved and stability of employment.
Disclosure statement: All authors have declared no conflicts of
interest.
157. UNDERSTANDING THE CHILD AND PARENT’S
PERSPECTIVES ON MULTIDISCIPLINARY INTERVENTIONS
FOR BENIGN JOINT HYPERMOBILITY SYNDROME
Background: Benign Joint Hypermobility Syndrome (BJH) is often
associated with significant muscle movement and development
problems. Many children miss extensive periods of schooling because
of their symptoms. There is little empirical evidence about unmet
patient needs in current treatments or barriers to treatment adherence
in BJH. Treatment needs may not be readily identifiable by children
and their families because presenting symptoms may reflect a
relatively wide range of psychosocial, as well as physical factors.
The family’s perception of symptoms and their understanding of the
condition may influence quality of life. This qualitative study (EMBIC)
explored how children and parents experienced their treatment within
a Randomized Control Trail (RCT) which compared a 10 week
multidisciplinary team (MDT) intervention with current usual treatment.
Methods: Families were recruited to the EMBIC study at their 3 month
assessment in the RCT. Single semi-structured interviews with 26
families explored their perceptions of treatment and adherence to
recommended exercises. Children aged 5-14 years receiving the
intervention and usual treatment were recruited though purposive
sampling of levels of reported pain and types of family demographics
to enhance the trustworthiness. A critical realist approach, seeking to
account for dominant and conflicting realities of families, guided
thematic analysis. Participant validation and researcher triangulation
were used to increase credibility.
Results: Families commonly reported experiencing relief and symptom validation on receiving a diagnosis of BJH. Families in both the
intervention and treatment as usual groups reported that having a
diagnosis motivated information- seeking, self-management and
improved their communication with schools. During the intervention,
while families had regular contact with the MDT, they reported
consistently high compliance with exercise regimes, but this reduced
post intervention. Children identified MDT treatment features which
motivated them to undertake exercise programmes and made
suggestions on how the treatment programme could be improved to
increase their motivation to undertake exercises. MDT interventions
which were found to have a major impact on the well-being of the
whole family were not always expensive. Families receiving usual
treatment, whilst relieved to have a diagnosis remained unsure of how
to manage their condition. Both groups remained anxious about long
term prognosis and would have welcomed further information on this.
Conclusions: An intensive 10-week MDT intervention enhanced the
well-being of all interviewed children and parents. This qualitative
evaluation of families in an RCT suggests that targeted interventions
can improve the well-being of the child in terms of movement, pain
management, interactions with the school and family emotional
welfare.
Disclosure statement: All authors have declared no conflicts of
interest.
iii109
158. DOES EXCLUSION OF THE ESR FROM JADAS AFFECT
VALIDITY IN THE ROUTINE CLINICAL SETTING?
Flora McErlane1,2, Michael W. Beresford2,3, Eileen M. Baildam3,
Wendy Thomson1, Kimme Hyrich1, Alice Chieng4, Joyce Davidson5,
Helen E. Foster6, Janet Gardner-Medwin5, Mark Lunt1 and
Lucy Wedderburn7
1
School of Translational Medicine, University of Manchester,
Manchester, United Kingdom; 2Institute of Child Health, University of
Liverpool, Liverpool, United Kingdom; 3Paediatric Rheumatology,
Alder Hey Children’s Hospital, Liverpool, United Kingdom;
4
Rheumatology, Royal Manchester Children’s Hospital, Manchester,
United Kingdom; 5Rheumatology, Royal Hospital for Sick Children,
Glasgow, United Kingdom; 6Rheumatology, Newcastle Medical
School, Newcastle, United Kingdom; 7Rheumatology Unit, Institute
of Child Health, London, United Kingdom
Background: Juvenile Arthritis Disease Activity Score (JADAS) is a
4 variable composite disease activity (DAS) score for JIA (including
active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/
child global (PGE) and ESR). ESR is not routinely measured in UK
clinical practice, thereby hampering the clinical feasibility of JADAS.
This study aims to determine whether exclusion of the ESR from
JADAS (labelled JADAS-3 variables) impacts on correlation with single
markers of DA in clinical practice, through application to a prospective
inception cohort of UK children presenting with new onset inflammatory arthritis.
Methods: JADAS 10, 27 and 71 and JADAS-3 variables 10, 27 and 71
were determined for all children in the Childhood Arthritis Prospective
Study (CAPS) with complete data available. Correlation of JADAS and
JADAS-3 with single markers of DA was determined for the whole
cohort and individual ILAR subtypes. All correlations were calculated
using Spearman’s rank statistic.
Results: 262/1238 visits had sufficient data for calculation of JADAS
(1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%)
ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and
64% were female.
Correlation of JADAS and JADAS-3 variables was high, both for the
whole cohort (0.82) and within individual ILAR subtypes. With the
exception of the ESR, correlations of JADAS and JADAS-3 with single
DA markers were similar; both for the whole cohort and within the ILAR
subtypes (see Table 1).
Conclusions: Correlation with single DA markers was very similar for
JADAS and JADAS-3 variables, both in the group overall and within the
ILAR subtypes. Correlation of JADAS-3 with the ESR was low but
correlation with all other surrogates for DA was at least as high as
JADAS.
Composite indices reflect disease activity more reliably than their
individual components. JADAS-3 may be a valid surrogate for DA in
the clinical setting when the ESR is unavailable. Further validation is
required to determine whether JADAS and JADAS-3 variables reflect
changes in DA over time.
TABLE 1 Spearman’s correlation between JADAS, JADAS-3 variables and
single markers of DA
AJC
PGA
PGE
ESR
Limited 71 JC
Parental pain
Childhood health assessment
questionnaire
JADAS
JADAS-3 variables
0.59
0.64
0.61
0.53
0.41
0.53
0.47
0.73
0.75
0.75
*0.07
0.48
0.61
0.56
*p > 0.05
Disclosure statement: All authors have declared no conflicts of
interest.
159. GLYCOSYLATION OF VITAMIN D BINDING PROTEIN
REDUCED IN JUVENILE IDIOPATHIC ARTHRITIS PATIENTS
AT RISK OF DISEASE EXTENSION
David S. Gibson1,2, Sorcha Finnegan1, Keri Newell2,
Alexandra Evans2, Gwen Manning3, Caitriona Scaife3,
Catherine McAllister1, Stephen R. Pennington3, Mark Duncan2,4,
Terry Moore5 and Madeleine Rooney1
1
Arthritis Research Group, Queen’s University Belfast, Belfast,
United Kingdom; 2Division of Endocrinology, Metabolism and
Diabetes, University of Colorado, Denver, Colorado, United States of
America; 3Proteome Research Centre, University College Dublin,
Dublin, Ireland; 4Obesity Research Center, King Saud University,
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Linda Birt1, Fiona Poland1, Alexander MacGregor2, Kate Armon2 and
Michael Pfeil3
1
School of Allied Health Professions, University of East Anglia,
Norwich, United Kingdom; 2Department of Rheumatology, Norfolk
and Norwich University Hospitals NHS Foundation Trust, Norwich,
United Kingdom; 3School of Nursing Sciences, University of East
Anglia, Norwich, United Kingdom
Wednesday 2 May 2012, 10.45 – 11.45
iii110
Wednesday 2 May 2012, 10.45 – 11.45
Riyadh, Saudi Arabia; 5Division of Adult and Pediatric Rheumatology,
Saint Louis University, St Louis, Missouri, United States of America
160. A NOVEL ASSAY FOR DETECTING NITRATED
NUCLEOSOMES: A POTENTIAL SURROGATE BIOMARKER
FOR JUVENILE ONSET SYSTEMIC LUPUS ERYTHEMATOSUS
Charis Pericleous1,3, Sara C. Croca1, Ian Giles1, Karim Alber1,
Harry Yong1, David Isenberg1, Angela Midgely2, Michael
W. Beresford2, Anisur Rahman1 and Yiannis Ioannou1,3
1
Adolescent Rheumatology, UCL, London, United Kingdom;
2
Paediatric Rheumatology, Alder Hey Children’s NHS Foundation
Trust Hospital, Liverpool, United Kingdom; 3Paediatric
Rheumatology, Institute of Child Health, London, United Kingdom
Background: Juvenile onset systemic lupus erythematosus (JSLE)
caries a poorer prognosis and has higher rates of nephritis as
compared to adult onset. Studies on adult SLE have shown that
oxidative and nitrosative stress correlate with disease activity. Antinucleosome antibodies are pathogenic and associate with lupus
nephritis. We have recently developed a novel serum based assay for
detecting nitrated nucleosomes, the levels of which correlate with
disease activity in adult onset SLE. Our hypothesis was that nitrated
nucleosomes would be significantly elevated in JSLE as compared to
adult SLE.
Methods: The assay is a sandwich-ELISA. Proteins with nitrated
tyrosine residues are captured on a streptavidin plate pre-coated with
a biotinylated anti-nitrotyrosine antibody. The presence of nitrated
nucleosomes are then detected by probing with a rabbit anti-histone-3
monoclonal antibody and subsequently with an HRP-conjugated antirabbit IgG antibody. This assay has an inter-plate and intra-plate
coefficient of variation of less than 10%. Serum samples form 49
patients with adult onset SLE were analysed versus 20 serum samples
from children with SLE.
Results: Adult onset SLE samples 41F:8M, age (mean SD)
35.9 12.8 years. JSLE samples 10F:10M, age 13.6 3.8 years.
Levels of nitrated nucleosome in adult SLE samples versus JSLE
samples were (mean SD) 29.37 53.5 units versus 227.1 902.2
units, p < 0.03. Analysing healthy control samples from 10 adult
volunteers versus 10 children, there was no evidence of increased
nitrated nucleosomes and no difference between the 2 groups (adult
versus children - mean SD 3.7 4.9 vs 13.3 23.3, p < 0.24).
Conclusions: There are elevated levels of nitrated nucleosomes in
samples from juvenile onset SLE patients as compared to adult onset
SLE. Further studies are underway to determine whether this is as a
consequence of increased activity, or whether nitration of this key
autoantigen may play an aetiopathogenic role in promoting antigenic
drive of pathogenic autoantibodies, which may account for the
differing prevalence of organ involvement observed in JSLE.
Disclosure statement: All authors have declared no conflicts of
interest.
PRIMARY CARE
161. THE COURSE OF COMORBID ANXIETY SYMPTOMS
IN PATIENTS PRESENTING TO GENERAL PRACTICE WITH
SYMPTOMATIC OSTEOARTHRITIS: LATENT CLASS
GROWTH ANALYSIS
Magdalena Rzewuska1, Christian Mallen1, Vicky Y. Strauss1,
John Belcher1 and George Peat1
1
Arthritis Research UK Primary Care Centre, Primary Care Sciences,
Keele University, Keele, United Kingdom
Background: Concurrent elevated anxiety symptoms are common in
people with symptomatic OA and contribute to levels of disability. Yet
it is unclear how often anxiety symptoms present at the time of seeking
formal healthcare for OA represent persistent states of anxiety and
what factors are associated with different anxiety symptom trajectories. An understanding of the natural course of anxiety symptoms in
patients with OA is required to inform clinicians, allocate healthcare
resources and improve patients’ awareness.
Methods: Participants were older adults consulting general practice
with symptomatic OA. Self-completion questionnaires, containing
measures of anxiety and depressive symptoms, age, gender, pain
status, coping and social status were mailed within 1 week of the
consultation and at 3, 6, 12 months. A person-centred approach
applying Latent Class Growth Analysis (LCGA) was used to identify
clusters of anxiety symptoms, which were ascertained with cut-off
score 8 on the Hospital Anxiety and Depression Scale anxiety
subscale. Associations between baseline characteristics and cluster
membership were examined using multinomial logistic regression
(entry probability p < 0.10).
Results: A 4-cluster LCGA anxiety model was supported in 293
participants with complete anxiety data. Clusters were: no anxiety
(41.3%), persistent (29.7%), unstable (19.1%) and progressive (9.9%)
anxiety. Catastrophizing, coping by increased behavioural activities,
pain extent and interference with work, occupational class and
perceived lack of instrumental support were differently associated
with four anxiety clusters (Table). Age, gender, other coping strategies
and factors related to social interactions showed no significant effects
on anxiety trajectories.
Conclusions: Sixty percent of patients with OA have reported nonnormal anxiety levels over 12 months. In addition, an estimated 60% of
patients with symptomatic OA presenting to general practice with
concurrent anxiety symptoms will experience persistent anxiety for at
least 12 months. Odds ratios suggest that coping by catastrophizing
(Adj. OR ¼ 4.25, 95% CI 0.24-0.83) and pain extent (Adj. OR ¼ 1.09,
95% CI 1.04-1.15) are most prominent factors associated with the
persistent anxiety trajectory.
TABLE 1 Backward elimination multinomial logistic regression analyses of baseline
covariates and trajectories of anxiety.
Covariates
Coping by catastrophizing
Coping by increased behavioural activities
Lack of instrumental support
Manual/routine occupational
class
Pain extent (total number of
pain sites 0-44)
Pain interference with work
(0–10)
a
A reference category.
‘Persistent’ vs.
‘No anxiety’a
Adj. OR (95%CI)
‘Unstable’ vs.
‘Progressive’ vs.
‘No anxiety’a
‘No anxiety’a
Adj. OR (95%CI) Adj. OR (95%CI)
4.25 (1.99, 9.06)
0.45 (0.24, 0.83)
4.04 (1.83, 8.95)
0.51 (0.27, 0.97)
0.93 (0.28, 3.08)
0.66 (0.27, 1.61)
5.49 (1.52, 19.81) 1.54 (0.31, 7.60)
1.47 (0.76, 2.81) 1.47 (0.75, 2.88)
3.35 (0.54, 20.82)
4.00 (1.60, 9.97)
1.09 (1.04, 1.15)
1.04 (0.98, 1.09)
1.08 (1.01, 1.15)
1.18 (1.05, 1.33)
1.12 (0.99, 1.26)
1.29 (1.08, 1.54)
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: Juvenile idiopathic arthritis (JIA) comprises a poorly
understood group of chronic, childhood onset, autoimmune diseases
with variable clinical outcomes. We investigated whether profiling of
the synovial fluid (SF) proteome by a fluorescent dye based, twodimensional gel (DIGE) approach could distinguish the subset of
patients in whom inflammation extends to affect a large number of
joints, early in the disease process. The post-translational modifications to candidate protein markers were verified by a novel
deglycosylation strategy.
Methods: SF samples from 57 patients were obtained around time of
initial diagnosis of JIA. At 1 year from inclusion patients were
categorized according to ILAR criteria as oligoarticular arthritis
(n ¼ 26), extended oligoarticular (n ¼ 8) and polyarticular disease
(n ¼ 18). SF samples were labeled with Cy dyes and separated by
two-dimensional electrophoresis. Multivariate analyses were used to
isolate a panel of proteins which distinguish patient subgroups.
Proteins were identified using MALDI-TOF mass spectrometry with
vitamin D binding protein (VDBP) expression and siaylation further
verified by immunohistochemistry, ELISA test and immunoprecipitation. Candidate biomarkers were compared to conventional inflammation measure C-reactive protein (CRP). Sialic acid residues were
enzymatically cleaved from immunopurified SF VDBP, enriched by
hydrophilic interaction liquid chromatography (HILIC) and analysed by
mass spectrometry.
Results: Hierarchical clustering based on the expression levels of a
set of 23 proteins segregated the extended-to-be oligoarticular from
the oligoarticular patients. A cleaved isoform of VDBP, spot 873, is
present at significantly reduced levels in the SF of oligoarticular
patients at risk of disease extension, relative to other subgroups
(p < 0.05). Conversely total levels of vitamin D binding protein are
elevated in plasma and ROC curves indicate an improved diagnostic
sensitivity to detect patients at risk of disease extension, over both
spot 873 and CRP levels. Sialysed forms of intact immunopurified
VDBP were more prevalent in persistent oligoarticular patient synovial
fluids.
Conclusions: The data indicate that a subset of the synovial fluid
proteome may be used to stratify patients to determine risk of disease
extension. Reduced conversion of VDBP to a macrophage activation
factor may represent a novel pathway contributing to increased risk of
disease extension in JIA patients.
Disclosure statement: All authors have declared no conflicts of
interest.
POSTER VIEWING II
POSTER VIEWING II
Disclosure statement: All authors have declared no conflicts of
interest.
162. PRIMARY CARE ATTITUDES TO METHOTREXATE
MONITORING
Rachel Byng-Maddick1, Madhavi Wijendra1 and Henry Penn1
1
Rheumatology, Northwick Park Hospital, London, United Kingdom
163. THE ASSOCIATION OF GOUT WITH SLEEP DISORDERS
AND SLEEP APNOEA: A CROSS-SECTIONAL
EPIDEMIOLOGICAL STUDY IN PRIMARY CARE
Edward Roddy1, Sara Muller1, Richard Hayward1 and
Christian Mallen1
1
Arthritis Research UK Primary Care Centre, Keele University,
Stoke-on-Trent, United Kingdom
Background: Both gout and obstructive sleep apnoea syndrome are
prevalent in primary care and are associated with considerable
comorbidity including the metabolic syndrome. Up to 50% of patients
with obstructive sleep apnoea syndrome also have hyperuricaemia.
Despite shared co-morbidities and risk factors, a possible association
between gout and obstructive sleep apnoea syndrome has not been
explored previously. The objectives of this cross-sectional epidemiological study were to determine, firstly, whether an association exists
between gout and obstructive sleep apnoea syndrome and other sleep
disorders and, secondly, whether any such association is independent
of comorbid traditional vascular risk factors and vascular disease.
Methods: Data were taken from a validated database of general
practice records from nine practices in the UK covering 64,747 adults
between 2001 and 2008. People consulting for gout were identified via
iii111
Read codes and each matched with four controls for age, gender,
practice and year of gout consultation. Sleep problems and confounding comorbidities were also identified via Read codes. Sleep
problems were first considered as the occurrence of any sleep
problem during the study period, and then sub-grouped into sleep
apnoea and non-sleep apnoea sleep disorders forming two mutually
exclusive sub-groups. Medications were categorized according to
British National Formulary codes and then identified in a linked
database of prescription records. Unadjusted odds ratios (OR) were
calculated for the association between gout and sleep disorders and
then adjusted for the presence of ischaemic heart disease, hypertension, diabetes mellitus and diuretic use using logistic regression
models.
Results: 1689 individuals with gout were identified: mean age was 63
years and 1292 (76%) were male. Each gout case was successfully
matched to four controls. Ischaemic heart disease, hypertension,
diabetes mellitus and diuretic use were each more prevalent in gout
cases than controls. In unadjusted analyses, gout was associated with
any sleep problem (OR 1.44; 95% confidence interval (CI) 1.11, 1.87),
non-sleep apnoea sleep problems (OR 1.36; 95%CI 1.03, 1.80) and
sleep apnoea (OR 2.10; 95%CI 1.01, 4.39). On multivariate analysis,
gout remained significantly associated with any sleep problem (OR
1.39; 95% CI 1.06, 1.81) and non-sleep apnoea sleep problems (OR
1.37; 95%CI 1.03, 1.82), but not sleep apnoea (OR 1.48, 95% CI 0.70,
3.14)).
Conclusions: Although the association between gout and sleep
apnoea did not appear to persist after adjustment for confounding
comorbidity, the two conditions appear to co-exist. Clinicians should
therefore be aware of gout as a cause of painful joints in patients with
sleep apnoea and also of the latter as a cause of excessive sleepiness
in patients with gout. Larger prospective epidemiological studies are
required to explore causality.
Disclosure statement: All authors have declared no conflicts of
interest.
164. ABSTRACT WITHDRAWN
165. MANAGEMENT OF GOUT IN A PRIMARY
CARE PRACTICE
Fawzi Kamlow1, Angela Pakozdi2 and Ali Jawad2
General Practice, The Burnham Surgery, Burnham-on-Crouch,
United Kingdom; 2Rheumatology, Barts and the London NHS Trust,
London, United Kingdom
1
Background: The most common inflammatory arthropathy presenting
to primary care practices is gout; and recent estimates have indicated
that the prevalence and incidence have been rising. Our aim was to
estimate the prevalence and to review the management of gout in
primary care and to improve prevention and treatment.
Methods: We analysed medical records of 9621 patients registered at
a primary care practice as of May 2011. Computer entries for any
patients with a diagnosis of gout were identified and their medical
records were studied. Data regarding co-morbidities, serum uric acid
levels (SUA), non-steroidal anti-inflammatory drug (NSAID), colchicine
and uric acid lowering drug prescriptions, and monitoring of
hyperuricaemia were obtained and analysed.
Results: 290(3%) of 9621 patients were identified with a diagnosis of
gout, 21% were female and 79% were male patients. 70.5% of female
patients were above age 65 and 26.2% were between age 45 and 65.
Among male patients, 51.3% were above age 65 and 42% were
between 45 and 65. Regarding their co-morbidities, 55.5% suffered
from hypertension, 29% had chronic kidney disease stage 3 and
above, 14.5% had diabetes and 48.6% had a body mass index above
30. SUA was recorded in 207 patients (71%). SUA was below
310 mmol/L in 6.8%, 311-360 mmol/L in 15.5%, 361-480 mmol/L in
42.5%, 481-540 mmol/L in 18.4%, 541-600 mmol/L in 10.6% and above
601 mmol/L in 6.3% of patients. 38.6% of patients were treated with
either NSAIDs or colchicine. 28.6% of patients were prescribed uric
acid lowering medication. In terms of SUA level monitoring, only
14.8% of patients had SUA measured within the past one year, 25.5%
within two years, 34.1% within three years and 43.8% within 5 years.
Conclusions: The prevalence of gout in our practice was found to be
3%, approximately twice higher than expected based on previous UK
national reports. In part, this could be explained by that diagnosis was
mostly based on clinical assessment, patient self-report or medical
records. The prevalence was found to be higher in men than in women
and increased with age. The frequency of co-morbidities among
patients with diagnosis of gout was surprisingly high. Only one third of
patients were treated for acute gout attack with NSAIDs or colchicine
by our practice, although self-treatment and secondary care treatment
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: Methotrexate (MTX) was discovered in the 1950s, and
approved for use in rheumatoid arthritis by the FDA in 1998. In 2006,
the National Patient Safety Agency issued a Safety Alert, following
increasing reports of prescribing errors and toxicity.
If taken at the right dose and with appropriate monitoring, oral
methotrexate is considered a safe and effective medication. Very
occasionally problems with taking the medication can cause serious
harm and even death. During the last ten years our hospital has seen
two deaths and other morbidity, directly relating to methotrexate use.
There are concerns that there are a wide variety of prescribing and
monitoring habits throughout our local primary care trusts. Poor
communication between primary and secondary care may lead to
inadequate monitoring - a safety concern, or duplication of monitoring
- cost implications.
We surveyed our local GP community to better understand their
practice, and to establish where patient care could be improved.
Methods: All GP practices in our local PCT (Brent) were sent a
standard questionnaire. Individual GP practices emailed by PCT chief
pharmacists twice, and non-responders were sent a postal copy.
Results were then collated after four months.
Results: 86 practices were contacted, and 31 responded (36% reply
rate). On average GPs have 1 patient on MTX per 743 patients in their
practice (0.13%). This ranged by practice from 0% to 0.5% of patients.
All GPs admitted that they were happy to repeat MTX prescriptions,
but only 77.4% were happy to monitor blood tests. The remainder
presumed to be monitored by the hospital.
Of those who did monitor, 58.6% were aware of the hospital’s
shared care guidelines and only 48.4% were aware of the BSR
guidelines. That left 26.7% of GPs monitoring and prescribing MTX
who were not aware of any monitoring guidelines.
70% of practices felt they did need further education on monitoring.
However 37.5% of those not aware of any guidelines did not feel they
needed further education.
Conclusions: The poor response rate in returning questionnaires may
indicate that Primary Care do not regard this subject as a priority area.
The low numbers of patients reported as being on MTX per practice
are surprising. This may reflect inadequate records, or under-diagnosis
(as it is anticipated 1% population have rheumatoid arthritis).
Serious safety concerns are raised from this data. Any doctor
prescribing MTX should be aware of how to monitor and appropriate
guidelines. Further education on diagnosis of RA and how to monitor
DMARDS should be instigated.
With this data we aim to encourage commissioners to fund a
computer monitoring system accessible in primary and secondary
care for improved patient safety, and to ultimately save on cost by
reducing duplication of work.
Disclosure statement: All authors have declared no conflicts of
interest.
Wednesday 2 May 2012, 10.45 – 11.45
iii112
Wednesday 2 May 2012, 10.45 – 11.45
could not be estimated. Concerning long term management, less than
a third were prescribed uric acid lowering medication and monitoring
of SUA levels was infrequent. To improve the care of patients suffering
from gout, we aim to set up a practice registry for patients suffering
from gout and to invite patients with SUA above 300 mmol/L for regular
consultations, to review co-morbidities and medication lists, and to
monitor treatment.
Disclosure statement: All authors have declared no conflicts of
interest.
166. FATIGUE AS A PRECURSOR TO POLYMYALGIA
RHEUMATICA: A RETROSPECTIVE COHORT STUDY
Daniel J. Green1, Sara Muller1, Christian Mallen1 and Sam L. Hider1
1
Primary Care Sciences, Arthritis Research UK Primary Care Centre,
Keele University, United Kingdom
167. COMMUNITY-BASED JOINT INJECTION CLINIC
Sarabjit Singh Bawa2 and Sandeep Bawa1
1
Dept of Rheumatology, Gartnavel General Hospital, Glasgow,
United Kingdom; 2Surgery, Glenboig, Lanarkshire, United Kingdom
Background: Over 30% of all GP consultations are due to
musculoskeletal (MSK) complaints. Currently, the present system
relies predominately on referral to secondary care in hospitals for most
conditions. However, access to these specialist services is limited in
some areas, and can result in long waiting times.
As a result patients endure undue pain, ill-health and time off work
whilst awaiting management of their complaints. There can be very
little management before a patient is seen in a consultant clinic which
can take up to 12 weeks.
Using the ‘‘MSK Framework’’ published by the Department of
Health as a foundation, we set up a multidisciplinary clinic within a
local population to try and improve access to specialist services and
reduce waiting times for those with MSK complaints.
Methods: A joint injection clinic was set up in Lanarkshire, Scotland,
serving a population of 52,913. The population is served by 28 GP’s.
The clinic was run from a local Health Centre, once a week for 1 hour,
where 12 patients were seen per clinic. Patient outcome was assessed
using a Visual Analogue Scale. A steering group was set up to oversee
the management of the clinic. The clinic was staffed by a GP,
physiotherapist, podiatrist, nurse, and a receptionist. Referrals were
taken from local GP’s, physiotherapists and podiatrists via a referral
form.
Results: During the period May ‘01 - March ‘10, 1946 patients were
referred to the clinic. (GP 84.2%; physio 8.5%; podiatry 6.8%;
unknown 0.47%; no source documented 22.7%)
In total 1535 pts were injected. 1361 received 1 injection, 299 2
injections, 68 3 injections. This involved 1738 injections.(Shoulder 683,
foot 347, elbow 295, knee 116, hand 98, hip 55, back 9, other 1, not
recorded 134). The most common reason for injection was rotator cuff
syndrome, tennis/golfers elbow and plantar fascitis. 406 patients did
not receive an injection
Over 88% of patients reported a greater than 50% improvement
in pain score, 54.7% returned to normal, 9.9% had a 30-50%
improvement, 1.9% no benefit. From the information available on
1396 patients, 1116 were discharged, 162 physiotherapy, 98 podiatry,
10 orthopaedics, 3 to other specialists.7 were sent for imaging.
Conclusions: To the best of our knowledge, our community based
joint injection clinic is the first of its kind in Scotland. Our results
highlight its success by providing high quality patient centred care.
The vast majority of patients were discharged from the clinic with
no further onward referral required (80%). This in turn shortens the
waiting time for those that do need to see a hospital consultant.
Our multidisciplinary interface clinic has provided an effective onestop shop for integrated care, provided shorter waiting times, early
diagnosis and treatment. Patients can thus return to work/lead an
active life sooner. There is less burden on the NHS finances(clinic
alone saved £300,000) The clinic also offers an expert multidisciplinary opinion for onward referral to specialist services.
Disclosure statement: All authors have declared no conflicts of
interest.
PSYCHOLOGY, MEASUREMENT AND
MANAGEMENT OF PAIN
168. DEVELOPMENT AND EVALUATION OF A COMPUTER
GRAPHICS APPLICATION FOR COMMUNICATING BODY
PERCEPTION IN PATIENTS WITH COMPLEX REGIONAL
PAIN SYNDROME
Ailie Turton1, Mark Palmer2, Sharon Grieve3, Jenny Lewis3,
Tim Moss1 and Candy McCabe1,3
1
Faculty of Health and Life Sciences, University of the West of
England, Bristol, United Kingdom; 2Faculty of Environment and
Technology, University of the West of England, Bristol,
United Kingdom; 3Bath Centre for Pain Services, Royal National
Hospital for Rheumatic Diseases, Bath, United Kingdom
Background: Patients with Complex Regional Pain Syndrome (CRPS)
experience distressing changes in body image. They often find it
difficult to describe their perceptions of affected body parts to
clinicians. Self portrait sketches are sometimes used, but this
method is limited by the individual’s capacity to draw. Computer
graphics offer an opportunity to provide an interactive tool to
communicate perceptions of body image. The purpose of this project
was to develop an application that patients will be able to use to create
a 3D model of their perceived body image.
Methods: Using data from a previous exploratory study of body
perception and consultation with a person with CRPS, the first
prototype digital media application was developed. The application
allows modification of an avatar to depict alterations in size, shape,
colour or visible surface texture of multiple body areas. It has so far
been tested with ten patients, admitted to an inpatient CRPS
rehabilitation programme, who gave consent to participate in the
research. Participants used the application in a consultation with the
research nurse. Audio recordings were made of the participants using
the application and participants were asked to complete a structured
questionnaire to ascertain their views and experience of using the tool.
Responses to questionnaires and audio recordings were subjected to
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: PMR is the commonest inflammatory disorder in
patients aged over 50 years and is largely managed in primary care.
It is characterized by bilateral shoulder and hip pain, morning stiffness
and elevated inflammatory markers. Whilst not a formal part of the
established diagnostic criteria, patients with PMR frequently complain
of fatigue. The aim of this study was to investigate whether PMR
patients are more likely to consult their GP with fatigue and sleeprelated symptoms than matched controls.
Methods: Consultation data were received from nine general practices
in North Staffordshire between 2000 and 2009. Consulters receiving a
Read-coded diagnosis of PMR were matched to 4 controls using age,
gender, GP practice and year of consultation. Fatigue and sleep were
defined using diagnostic Read codes. Cox regression was used to
determine association between PMR diagnosis and fatigue or sleep
disorder. The number of and timing of these consultations was
investigated using the multiple failure survival method of Anderson and
Gill. Robust standard errors were used to allow for matching.
Results: 561 PMR patients were identified. The mean (SD) age was
73.2 (9.6) years, 71% of participants were female. Patients were under
observation for 4.54 (SD ¼ 3.1) years until a PMR diagnosis was
recorded and observed on average for 5.45 (SD ¼ 3.1) years following
diagnosis.
Patients who consulted with fatigue were more likely to be female
(79% consulters compared to 70% non-consulters (p-value ¼ 0.007))
but no statistical difference in age of consulters was found. Prediagnosis, 35 cases (6.2%) and 81 controls (3.6%) consulted with
fatigue (p-value ¼ 0.009). Post-diagnosis, 23 cases (4.1%) and 75
controls (3.3%) consulted with fatigue (p-value ¼ 0.370). PMR was
associated with significantly more multiple fatigue consultations before
(HR ¼ 2.06, 95% CI (1.34-3.18)), but not after (HR ¼ 1.58 (0.91-2.74))
PMR diagnosis.
No association was seen between sleep disorders and PMR
diagnosis with 16 PMR cases (2.9%) and 56 (2.5%) controls consulting
before diagnosis (p-value ¼ 0.654) and 15 cases (2.7%) and 60
controls (2.7%) consulting post diagnosis (p-value > 0.999). No
association was observed between multiple consultations for sleep
problems either pre (HR ¼ 1.83 (0.88-3.82)) or post PMR diagnosis
(HR ¼ 0.65 (0.34-1.23)).
Conclusions: Patients diagnosed with PMR in primary care are
significantly more likely to have consulted for fatigue but not sleep
disorders before their PMR diagnosis. This suggests GPs should be
considering PMR as a potential diagnosis in patients with multiple
fatigue consultations.
Disclosure statement: All authors have declared no conflicts of
interest.
POSTER VIEWING II
POSTER VIEWING II
169. AN INVESTIGATION OF PSYCHOLOGICAL
CHARACTERISTICS LINKED TO PHYSICAL ACTIVITY AND
SLEEP IN RHEUMATOID ARTHRITIS
Claire E. Goodchild1, Nicole Tang1,2, David Scott3 and
Paul Salkovskis1,4
1
Psychology, Institute of Psychiatry, King’s College London, London,
United Kingdom; 2Arthritis Research UK Primary Care Centre, Keele
University, Keele, United Kingdom; 3Academic Department of
Rheumatology, The Medical School, King’s College London, London,
United Kingdom; 4Psychology, University of Bath, Bath,
United Kingdom
Background: Impaired physical activity and sleep disturbance are
prevalent in RA and restrict daily functioning. Research is needed to
identify psychological processes associated with physical activity and
sleep in RA, which may exacerbate disability. Literature concerning
chronic pain has indicated that health focused anxiety, catastrophic
thinking, rumination (repetative worrying) and a sense of mental defeat
are linked to physical disability and sleep disturbance. These cognitive
processes have not yet been assessed in RA but may have important
implications considering pain is an important symptom for this
population. The aim of this study was to assess the presence of
specific psychological processes in RA and examine associations with
physical activity, sleep and other disability-related variables.
Methods: Participants were 135 adults (aged between 18 and 65
years) with established RA (diagnosis of at least 2 years) who were
receiving stable treatment. Participants’ level of physical activity was
measured using the International Physical Activity Questionnaire
(IPAQ; Booth, 2000) and sleep disturbance was assessed using the
Insomnia severity Index (ISI; Bastien, Vallie`res, Morin, 2001).
Participants also completed the Pain Self Perception Scale (Tang
et al., 2006), Short Health Anxiety Inventory (Salkovskis, Rimes,
Warwick, Clark, 2002), Pain Catastrophizing Scale (Sullivan, Bishop,
Pivik, 1995), Rumination-Reflection Questionnaire (Trapnell &
Campbell, 1999), Hospital Anxiety and Depression Scale (Zigmond &
Snaith, 1983), Health Assessment Questionnaire (Kirwan & Reeback,
1986), Brief Pain Inventory (Cleeland, 1989), and Profile of Fatigue
(Bowman, Booth, Platts, 2004).
Results: There were significant positive correlations between the
psychological process variables and pain, sleep, impaired functioning
and fatigue (r ¼ 0.19-0.38). Physical activity was negatively associated
with health anxiety (r ¼ -0.28) and depression (r ¼ -0.27). In a series of
stepwise regression analyses, mental defeat emerged as a significant
predictor of impaired functioning, whereas anxiety predicted sleep
interference and health anxiety predicted physical activity.
Conclusions: These findings suggest that psychological processes,
such as mental defeat and health anxiety, may play an important role in
the development and maintenance of disability associated with RA.
Addressing these psychological processes may improve quality of life
for those struggling to manage RA.
Disclosure statement: All authors have declared no conflicts of
interest.
iii113
170. GOOD SLEEP HYGIENE MAY IMPROVE PAIN IN
INFLAMMATORY ARTHRITIS
Shilpa Selvan1 and Lyn Williamson1
1
Rheumatology, Great Western Hospital, Swindon, United Kingdom
Background: Sleep problems are common and contribute to joint
pain, stiffness and fatigue in patients with inflammatory arthritis. As a
consequence, this may even lead to escalation of immunomodulatory
therapies. We studied factors affecting sleep outside of mood and
disease activity in a cohort of rheumatology patients.
Methods: All rheumatology patients on our DMARD monitoring
database were invited by letter to complete an anonymous questionnaire about sleep, asking about sleep interruption, sleep quality,
effect of daytime sleepiness on concentration, mental and physical
function, sleep posture, sleep aiding medications, caffeine and alcohol
intake.
Results: Of 1331 patients invited, 605 (46%) replied of whom 402
(67%) were female. Patients had the following diagnoses: rheumatoid
arthritis 381; psoriatic arthritis 67; ankylosing spondylitis 21; other
inflammatory rheumatological conditions 122. 540 (89%) patients
reported interrupted sleep, compared with 41% in a general population from the literature (p < 0.0001). 246 (53%) patients reported
daytime sleepiness affecting concentration, mental function and
physical function. 168 patients reported poor concentration on a
daily basis. Of these, 97 (57%) reported poor sleep posture compared
with 46 of 426 (11%) patients with good sleep posture (p < 0.0001).
143 (24%) patients reported poor sleep posture and 59 (10 %) had
received advice about sleep posture. Of those that had not received
advice, 278 (53%) felt this would be helpful. 539 (89%) drank
caffeinated drinks, mean 4.7 (range 1-28) cups daily. 53 (9%) drank
no caffeinated drinks. Mean alcohol intake was 1.7 (range 1–30) units
weekly, with 25 (4%) regularly drinking alcohol to fall asleep.
Conclusions: Our study confirms the importance of sleep issues in
inflammatory arthritis patients. Half our patients reported daytime
sleepiness affecting mental function, physical function and concentration. Factors other than disease activity and sleep posture and mood,
caffeine and alcohol intake, and bladder dysfunction may also affect
sleep quality. These should be addressed in routine consultations, as
optimization of sleep may reduce the need for immunomodulatory
medication, and improve patient quality of life.
Disclosure statement: All authors have declared no conflicts of
interest.
171. A MIND MAP FOR SLEEP FOR ARTHRITIS PATIENTS
Shilpa Selvan1 and Lyn Williamson1
1
Rheumatology, Great Western Hospital, Swindon, United Kingdom
Background: There is considerable evidence for the correlation
between poor sleep patterns and pain in inflammatory arthritis
patients. Causes of poor sleep are multifactorial and include disease
activity, mood disturbance, and medications such as steroids. Nonclinical factors such as sleep posture, sleep hygiene, caffeine and
alcohol intake and bladder disturbance adversely affect sleep, but are
not easily addressed in routine consultations because of time
constraints and lack of readily available information.
Methods: We designed a simple mind map for sleep to complement
the available written information leaflets (e.g Arthritis Research UK).
The map was designed on one side of A4, and folded into 3 sections.
Results: The pictorial side included three main domains: factors to
address before bedtime (e.g. reading, listening to restful music, good
pain control, herbal remedies including valerian and camomile tea,
relaxation techniques including stretches and breathing exercises);
environmental factors (e.g. comfortable bedding, correcting the
surrounding temperature, sleeping in a quiet and dark environment);
factors to avoid prior to sleep (e.g. smoking, alcohol, caffeine, late
evening heavy or spicy foods, late evening exercise).
The reverse has three sections combining diagrams and simple
written information: relaxing exercises prior to sleep; correcting sleep
posture; helpful general advice to aid sleep.
We validated the readability and usefulness of our mind map in
rheumatology outpatient and general practice settings. Of 65
rheumatology patients asked, 58 (89%) agreed it was readable, 52
(80%) agreed it was useful, and 53 (82%) agreed it was well designed.
Of 50 patients asked in general practice, 43 (86%) agreed it was
readable, 47 (94%) agreed it was useful and 42 (84%) agreed it was
well designed.
Conclusions: Good sleep is important in arthritis patients. We present
a ‘mind map for sleep’ leaflet for patient education and advice on nonclinical factors around sleep. This will optimize outpatient consultation
time whilst helping to address a common, important and sometimes
complex clinic problem.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
content analysis to determine acceptability of the application and its
limitations.
Results: The images produced by all ten participants are powerful
illustrations of the distortions in body perception that patients with
CRPS experience. Here is one striking example of a participant’s
reaction to her experience of using creating her body perception
image:
‘‘. . . it was quite bizarre seeing a picture of how exactly I feel as a
person, cause I’ve never had the opportunity of looking at that,
like that’’
‘‘It puts it into perspective what I’ve got, its just I don’t know how to
explain it. It looks in human form exactly how I feel and I’ve never had
that. I’ve sat and said this hand feels longer and feels wider from there.
I know I can see it but this is the first time someone else’’
All participants reported using the tool was an acceptable method
for communicating their body perception. It was considered better
than the drawings they currently use in interviews with the
Occupational Therapist. There were some additional features they
identified to improve the usability of the application.
Conclusions: This is the first time body perception has been captured
satisfactorily. The images created were far more descriptive than the
drawings used in current practice within a clinical interview. Further
development is planned to extract measurements from images.
Disclosure statement: All authors have declared no conflicts of
interest.
Wednesday 2 May 2012, 10.45 – 11.45
iii114
Wednesday 2 May 2012, 10.45 – 11.45
Disclosure statement: All authors have declared no conflicts of
interest.
172. THE EFFECT OF VITAMIN D LEVELS ON THE
ASSESSMENT OF DISEASE ACTIVITY IN RHEUMATOID
ARTHRITIS AND THE COMPONENTS OF THE DISEASE
ACTIVITY SCORE
Nishanthi Thalayasingam1,2, Matthew Higgins2,3,
Vadivelu Saravanan2, Martin Rynne2, Jennifer D. Hamilton2,
Carol Heycock2 and Clive Kelly2
1
Northern Deanery, Newcastle upon Tyne, United Kingdom;
2
Rheumatology, Queen Elizabeth Hospital, Gateshead,
United Kingdom; 3Medical School, Newcastle University, Newcastle
upon Tyne, United Kingdom
References
1. Cutolo M et al. Vitamin D involvement in rheumatoid arthritis and
systemic lupus erythematosus. Ann Rheum Dis 2009;68:446–447.
2. Mouyis M et al. Hypovitaminosis D among rheumatology outpatients in clinical practice. Rheumatology 2008;47:1348–51.
3. Rossini M et al. Vitamin D deficiency in rheumatoid arthritis:
prevalence, determinants and associations with disease activity
and disability. Arthritis Res Ther 2010;12:R216.
173. THE SYNCHRONOUS RELATIONSHIP BETWEEN
SOMATIC SYMPTOMS AND PSYCHOLOGICAL DISTRESS
IN EARLY RHEUMATOID ARTHRITIS: FINDINGS FROM A
PROSPECTIVE OBSERVATIONAL STUDY
Sam Norton1, Amanda Sacker2, John Done3 and Adam Young4
1
Institute of Public Health, University of Cambridge, Cambridge,
United Kingdom; 2Institute for Social & Economic Research,
University of Essex, Colchester, United Kingdom; 3School of
Psychology, University of Hertfordshire, Hatfield, United Kingdom;
4
Rheumatology Department, City Hospital, St Albans,
United Kingdom
Background: The longitudinal relationship between somatic symptoms and psychological distress in rheumatoid arthritis (RA) is often
assumed to be strong and bidirectional. However, despite previous
research identifying strong cross-sectional associations, only weak
longitudinal associations have been observed. This may be due to the
failure to differentiate the impact of symptoms relating to underlying
disease progression on distress, from symptoms relating to disease
flare. Using data from a prospective observational study, synchronous
changes in distress and symptoms of pain and functional limitation
over 5 years are assessed, differentiating between the impact of
disease progression and disease-flare.
Methods: Psychological distress, assessed by the Hospital Anxiety
and Depression Scale (HADS) total score, was recorded annually from
diagnosis in 784 patients (67% female, mean age at onset 57.0 yrs)
enrolled in a multi-centre inception cohort (ERAS). Pain was assessed
by visual analogue scale and function by the Health Assessment
Questionnaire (HAQ). Longitudinal changes in pain, function and
distress were modelled using multivariate autoregressive latent
trajectory analysis. This approach combines random effects for
heterogeneity in change (underlying disease progression) with an
autoregressive structure to account for deviations from this trajectory
(disease flare).
Results: Cross-sectionally pain, HAQ, and distress were moderately
to strongly related across the 5 years of follow up (r ¼ .28 to .57).
Reflecting the initiation of disease-modifying therapy, improvements
were observed between baseline and 1 year for pain ( ¼ -19.3,
p < .001), function ( ¼ -.29, p < .001) and distress ( ¼ -1.52,
p < .001). Between 1 and 5 years pain, function and distress
deteriorate significantly (average yearly change: pain ¼ 0.64 [95%
CI: 0.09, 1.19]; HAQ ¼ .034 [95% CI: 0.029, 0.039]; HADS ¼ 0.12
[95% CI: 0.01, 0.25]). Furthermore, changes in pain and function were
highly related to changes in distress (r ¼ .46 & .44, respectively),
suggesting changes in distress mirror underlying disease progression.
Significant autoregressive effects were observed for pain and function
( ¼ .22 & .28, respectively), indicating an effect of disease flare on the
propensity for worse pain and function at later time-points. No such
effect was observed for distress. However, function predicted the rate
of change in distress (b ¼ .20, p < .01), identifying it as a driver for
changes in distress and a key target for intervention.
Conclusions: Accounting for underlying disease progression,
changes in distress and somatic symptoms in RA are highly related.
While disease flare impacts on later pain and function it does not lead
to higher future distress. These findings suggest targeting somatic
symptoms will aid long-term psychological well-being as well as health
related quality of life in general.
Disclosure statement: All authors have declared no conflicts of
interest.
RHEUMATOID ARTHRITIS: TREATMENT
174. TREATING RHEUMATOID ARTHRITIS TO TARGET:
OUTCOMES AND PREDICTORS IN EARLY RHEUMATOID
ARTHRITIS PATIENTS TREATED WITH ADALIMUMAB
PLUS METHOTREXATE, METHOTREXATE ALONE OR
METHOTREXATE PLUS SUBSEQUENT ADALIMUMAB
Josef S. Smolen1, Roy M. Fleischmann2, Paul Emery3,
Ronald F. van Vollenhoven4, Benoıˆt Gue´rette5, Sourav Santra6,
Hartmut Kupper7, Laura Redden6 and Arthur Kavanaugh8
1
Department of Rheumatology, Medical University of Vienna and
Hietzing Hospital, Vienna, Austria; 2Department of Medicine,
University of Texas-Southwestern, Dallas, Texas, United States of
America; 3Department of Rheumatology, Leeds Teaching Hospital,
Leeds, United Kingdom; 4Department of Rheumatology, The
Karolinska Institute, Stockholm, Sweden; 5GPRD, Abbott, Rungis,
France; 6GPRD, Abbott, Abbott Park, Illinois, United States of
America; 7GPRD, Abbott GmbH & Co, Ludwigshafen, Germany;
8
Department of Rheumatology, University of California at San Diego,
La Jolla, California, United States of America
Background: The goals were to compare 78-wk outcomes in pts who
continued methotrexate (MTX) or adalimumab (ADA) þ MTX after
reaching a stable target (DAS28 < 3.2, LDA) at wk 22&26, and to
evaluate open-label (OL) ADA þ MTX in MTX-pts who did not achieve
the target.
Methods: MTX-naı¨ve pts 18 years with RA<1 year, DAS28(CRP)
>3.2, ESR 28 mm/hr or CRP 1.5 mg/dL, and either >1 erosion,
RFþ, or anti-CCPþ were randomized to ADA þ MTX (n ¼ 515) or
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: Interest in the role of vitamin D in rheumatic disease has
developed apace with reports that low levels of vitamin D may be
associated with inflammatory joint disease and other autoimmune
disorders[1]. Indeed, low levels of vitamin D have been reported in
different rheumatic disease processes, including rheumatoid arthritis
(RA)[2]. Disease activity in RA is assessed by a combination of
objective and subjective tests, combined to produce a disease activity
score in 28 joints (DAS28). There is some evidence that RA disease
activity, assessed by DAS28, can be influenced by vitamin D levels[3].
This could be due to a true immunomodulatory effect of vitamin D or a
more subjective effect of low vitamin D on pain perception. We
address this issue by comparing vitamin D levels with disease activity
and analysing each component of the DAS28 score separately.
Methods: We measured 25-hydroxy vitamin D levels in 126
consecutive RA outpatients and recorded a DAS28 score using an
ESR checked at the same time. We calculated DAS28 both with and
without the patient’s rating of joint pain on the Visual Analogue Score
(VAS) to assess the effect of VAS on DAS28. The vitamin D results
were expressed as nmol/l with 50 nmol/l taken as the lower limit of
normal. We calculated the correlation between vitamin D levels and
DAS28 for the group and then recorded the correlation between
vitamin D and each component of DAS28.
Results: The overall mean DAS28 score was 3.58 (SEþ/-0.13) and the
mean vitamin D level was 40.15 nmol/l (SEþ/-1.81). There was no
significant correlation between vitamin D and DAS28 scores with or
without the inclusion of VAS. However, there was a significant
correlation between vitamin D and VAS itself (r ¼ -0.20, p ¼ 0.027).
There was no correlation found between vitamin D level and ESR,
tender or swollen joint counts.
Conclusions: Our data confirms that vitamin D deficiency is common
in RA. We provide evidence that the VAS component, assessing
patient perception of joint pain, is related to vitamin D; with lower levels
producing higher VAS values. Although there was no overall correlation
between vitamin D levels and DAS28, patients may be assessed as
responding less well to disease modification in the presence of vitamin
D deficiency. This could have major implications for subsequent
management and clinicians should be aware of the potential
confounding effect of vitamin D deficiency in the assessment of RA
disease activity using the full DAS28 tool.
Disclosure statement: All authors have declared no conflicts of
interest.
POSTER VIEWING II
POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
TABLE 1 Clinical, functional, and radiographic outcomes at week 78
Treatment
group
DAS28 < 3.2 ACR
and mTSS 20/50/70,
0.5(a), % %
ADA þ MTX(R)! 70
ADA þ MTX
PBO þ MTX(R)! 55
PBO þ MTX
P value
.02
DAS28 DAS28 HAQ-DI mTSS
<3.2, % <2.6, % <0.5, % 0.5(b),
%
95/89/77
91
86
67
89
91/77/62
81
68
64
78
.002
.71
.02
.23/.03/.01 .03
175. INITIAL COMBINATION THERAPY WITH ADALIMUMAB
PLUS METHOTREXATE LEADS TO BETTER LONG-TERM
OUTCOMES IN PATIENTS WITH ADVANCED RHEUMATOID
ARTHRITIS: ANALYSIS OF THE FINAL 10-YEAR RESULTS
OF AN OPEN-LABEL EXTENSION OF A PHASE 3 TRAIL
Edward C. Keystone1, Desiree van der Heijde2, Michael
E. Weinblatt3, Neelufar Mozaffarian4, Benoıˆ t Gue´rette5,
Hartmut Kupper6, Shufang Liu4 and Arthur Kavanaugh7
1
Department of Medicine, University of Toronto, Toronto, Ontario,
Canada; 2Department of Rheumatology, Leiden University Medical
Center, Leiden, Netherlands; 3Division of Rheumatology,
Immunology and Allergy, Brigham and Women’s Hospital, Boston,
Massachusetts, United States of America; 4GPRD, Abbott, Abbott
Park, Illinois, United States of America; 5GPRD, Abbott, Rungis,
France; 6GPRD, Abbott GmbH & Co KG, Ludwigshafen, Germany;
7
Department of Rheumatology, University of California at San Diego,
La Jolla, California, United States of America
Background: DE019 was a phase 3, randomized, controlled trial (RCT)
in which patients with active, advanced rheumatoid arthritis (RA) and
inadequate response to methotrexate (MTX) were randomized to 1
year of adalimumab (ADA) 40-mg-every-other-week (eow), ADA 20mg-weekly, or placebo (PBO) injections; all received concomitant
MTX. RCT results demonstrated the clinical and radiographic superiority of ADA þ MTX over PBO þ MTX. All patients completing year-1
were eligible to receive open-label (OL) ADA 40-mg-eow þ MTX for an
additional 9 years. This post hoc analysis evaluated whether a 1 year
delay in initiation of ADA treatment results in differences in clinical,
functional, or radiographic efficacy after up to 10 years of treatment.
Methods: Outcomes included: clinical, [DAS28(CRP)], functional,
(HAQ-DI); radiographic damage, (mTSS) at baseline (BL) and year-1,
-8, and -10, with progressors defined as change () in mTSS from
BL > 0.5. Differences in mean mTSS between initial treatment arms
were assessed using a constrained longitudinal data analysis. Safety
was assessed in terms of adverse events for all patients exposed to
ADA.
Results: 619 patients were randomized; 202 (32.6%; 80/66/56
patients from the initial ADA 40-mg-eow/ADA 20-mg-weekly/PBO
arms, respectively) continued on OL ADA þ MTX through year-10.
Efficacy outcomes at year-10 were not different between the 2 ADA
arms; therefore, results for ADA 40-mg-eow are presented as
representative of ADA treatment. Switching to OL ADA þ MTX resulted
in resolution at year-10 of significant differences in responses
observed during year-1 between initial ADA and PBO arms: year-1
DAS28 ¼ 3.4/4.5, year-10 DAS28 ¼ 2.4/2.7 (ADA/PBO arms, respectively); likewise, year-1 HAQ-DI ¼ 0.8/1.1, year-10 HAQ-DI ¼ 0.7/0.8.
Rates of radiographic progression became comparable between
treatments during OL ADA þ MTX treatment (P ¼ .22). However,
patients initially randomized to ADA had significantly lower mean
mTSS compared with patients initially randomized to PBO (0.7 vs
6.2; P ¼ .005), and fewer patients with radiographic progression
(49.4% vs 61.1%). No new safety signals arose following up to 10
years of ADA exposure; there was perhaps a trend towards fewer
deaths than expected from a matched population [SMR (95%
CI) ¼ 0.77 (0.52-1.10)].
Conclusions: Patients with long-standing RA with up to 10 years of
ADA þ MTX treatment experienced safe and effective disease control.
Initial treatment with ADA led to better outcomes than with PBO, but
the disparities in clinical and functional response rates observed
during the RCT were largely ameliorated after treatment with OL
ADA þ MTX. Notably, radiographic damage remained lower in patients
initially randomized to ADA, owing to more extensive damage accrued
during the RCT in PBO-treated patients.
Disclosure statement: B.G. is an employee of, and possible stock/
option holder in, Abbott. A.K. has received consultancy fees or other
remuneration from Abbott. E.K. received research grants from Abbott,
Amgen, AstraZeneca, Bristol-Myers Squibb and Centocor, consultancy fees or other remuneration from Abbott, AstraZeneca, Biotest,
Bristol-Myers Squibb, Centocor, F Hoffmann-LaRoche, Genentech,
Merck, Nycomed, Pfizer and UCB, and is a member of the speakers
bureaus of Abbott, Bristol-Myers Squibb, F Hoffman-LaRoche, Merck,
Pfizer and UCB. H.K. is an employee of, and possible stock/option
holder in, Abbott. S.L. is an employee of, and possible stock/option
holder in, Abbott. N.M. is an employee of, and possible stock/
option holder in, Abbott. D.V. received research grants from Abbott,
Amgen, AstraZeneca, BMS, Centocor, Chugai, Eli Lilly, GSK, Merck,
Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough,
UCB and Wyeth, and consultancy fees or other remuneration from
Abbott, Amgen, AstraZeneca, BMS, Centocor, Chugai, Eli-Lilly, GSK,
Merck, Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, ScheringPlough, UCB and Wyeth. M.W. received research grants and
consultancy fees or other remuneration from Abbott.
176. DOES METHOTREXATE INCREASE THE RISK OF
VARICELLA OR HERPES ZOSTER INFECTION IN PATIENTS
WITH RHEUMATOID ARTHRITIS? A SYSTEMATIC
LITERATURE REVIEW
Natalie Zhang2, Sarah Wilkinson2, Mehmmod Riaz2, Andrew
J. Ostor1 and Muhammad K. Nisar1
1
Rheumatology, Addenbrookes Hospital, Cambridge,
United Kingdom; 2School of Clinical Medicine, University of
Cambridge, Cambridge, United Kingdom
Background: Methotrexate is the most commonly prescribed DMARD
for RA however a reluctance to prescribe this persists due to the
possible association with infections including varicella zoster virus
(VZV) and herpes zoster (HZ). In addition, no consensus exists
regarding pre-MTX VZV screening or the use of the VZ vaccine.We
review the current evidence for the risk of VZV and HZ infection in RA
patients receiving MTX and suggest best practice for pre-MTX VZV
screening and vaccination of non-immune patients.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
PBO þ MTX (n ¼ 517) for 26 wks (Period 1, P1). Responder pts (R)
continued
original
treatment
[ADA þ MTX(R)!ADA þ MTX,
PBO þ MTX(R)!PBO þ MTX] for an additional 52 wks (P2) and were
assessed for the primary outcome of DAS28 < 3.2 and mTSS 0.5 at
wk 78. PBO þ MTX inadequate responders (IR) received OL
ADA þ MTX after wk 26 [PBO þ MTX(IR)!OL ADA þ MTX].
Responses after 26 wks of OL ADA þ MTX were compared with the
P1 ADA þ MTX group. Regression analysis examined variables at
baseline (BL) and wk 12 with wk 26 rapid radiographic progression
(RRP, mTSS > 1.5). Pts were monitored for adverse events (AEs).
Results: After 26 wks, significantly more ADA þ MTX than PBO þ MTX
pts (44% vs 24%, P < 0.01) achieved the stable target at wks 22&26,
and high levels of response at wk 78 (Table 1). Mean mTSS
was persistently low (0.4, PBO þ MTX(R)!PBO þ MTX; 0.1,
ADA þ MTX(R)!ADA þ MTX). PBO þ MTX(IR)!OL ADA þ MTX pts
had responses comparable to pts initiated on ADA þ MTX but higher
mean mTSS (1.3 vs. 0.15); OL ADA addition reduced radiographic
progression in P2. BL CRP, anti-CCP, and erosions, and pt global at
wk 12 were predictive of RRP at 26 wks among PBO þ MTX(IR). AEs [n
(%)] in 863 pts with any exposure to ADA: SAEs, 99 (11.5); serious
infections, 33 (3.8); malignancies, 10 (1.2) including NMSC, 4 (0.5);
opportunistic infections (excluding TB), 7 (0.8); confirmed TB, 3 (0.3);
deaths, 9 (1.0).
Conclusions: Achieving a stable LDA target defined pts with good
prognosis. After 26 wks of inadequate MTX, adding ADA reduced
radiographic progression and yielded outcomes comparable with
naı¨ve pts initiated on ADA þ MTX, suggesting that rapid adjustment of
therapy in early RA may be comparable with initiation of ADA þ MTX.
Pts with poor prognostic factors may benefit from earlier use of
ADA þ MTX.
All outcomes are LOCF, unless otherwise indicated. (a) Primary
endpoint of study; non-responder imputation. (b) Multiple imputation.
Abbreviations: Wk, week; DAS28, 28-joint disease activity score;
mTSS, modified total Sharp score; ACR, American College of
Rheumatology; HAQ-DI, disability index of the health assessment
questionnaire; ADA, adalimumab; MTX, methotrexate; R, responder;
PBO, placebo.
Disclosure statement: P.E. has received consultancy fees or other
remuneration from Pfizer, Merck, Abbott, Roche, BMS. R.F. has
received consultancy fees or other remuneration from Abbott. B.G. is
an employee of, and possible stock/option holder in, Abbott. A.K. has
received consultancy fees or other remuneration from Abbott. H.K. is
an employee of, and possible stock/option holder in, Abbott. L.R. is an
employee of, and possible stock/option holder in, Abbott. S.S. is an
employee of, and possible stock/option holder in, Abbott. J.S.
received research grants and consultancy fees or other remuneration
from Abbott. R.V. received research grants from Glaxo Smithkline,
Merck, Pfizer, Roche and UCB, and consultancy fees or other
remuneration from Abbott, Glaxo Smithkline, Merck, Pfizer and Roche.
iii115
iii116
Wednesday 2 May 2012, 10.45 – 11.45
POSTER VIEWING II
TABLE 1 Overview of adverse events (E[E/100PYs]) over more than 5 years of therapy with ADA
Overall N ¼ 6610
(18272 PYs)
Time windows after first injection of ADA
0.5 yr N ¼ 6610
(3059 PYs)
Serious AEs
Fatal AEs
Serious infections
TB(a)
Sepsis
Malignancies(b)
Lymphoma
NMSC
Serious CHF
Cerebrovascular AEs
Serious haematologic AEs
Serious hepatic events
2529
102
518
35
35
121
15
43
47
56
13
58
(13.8)
(0.6)
(2.8)
(0.2)
(0.2)
(0.7)
(0.1)
(0.2)
(0.3)
(0.3)
(0.1)
(0.3)
838
29
162
11
13
19
1
8
15
13
4
10
>0.5 to 1 yr N ¼ 5922
(2256 PYs)
(27.4)
(0.9)
(5.3)
(0.4)
(0.4)
(0.6)
(<0.1)
(0.3)
(0.5)
(0.4)
(0.1)
(0.3)
419 (18.6)
19 (0.8)
83 (3.7)
11 (0.5)
4 (0.2)
16 (0.7)
0
2 (0.1)
6 (0.3)
5 (0.2)
2 (0.1)
13 (0.6)
>1 to 3 yrs N ¼ 4283
(6149 PYs)
661
27
154
8
7
45
9
17
12
16
1
16
(10.7)
(0.4)
(2.5)
(0.1)
(0.1)
(0.7)
(0.1)
(0.3)
(0.2)
(0.3)
(<0.1)
(0.3)
>3 to 5 yrs N ¼ 2623
(4549 PYs)
417
17
81
4
7
25
4
11
13
15
3
13
(9.2)
(0.4)
(1.8)
(0.1)
(0.2)
(0.5)
(0.1)
(0.2)
(0.3)
(0.3)
(0.1)
(0.3)
>5 yrs N ¼ 2000
(2260 PYs)
194
10
38
1
4
16
1
5
1
7
3
6
(8.6)
(0.4)
(1.7)
(<0.1)
(0.2)
(0.7)
(<0.1)
(0.2)
(<0.1)
(0.3)
(0.1)
(0.3)
CHF, congestive heart failure; E, events; NMSC, non-melanoma skin cancer; PYs, patient-years; TB, tuberculosis. (a) Including 2 pts with a positive test for latent TB during
ADA therapy. (b) Excluding lymphoma and NMSC.
177. SAFETY AND EFFECTIVENESS OF ADALIMUMAB IN
PATIENTS WITH RHEUMATOID ARTHRITIS DURING MORE
THAN 5 YEARS OF THERAPY OBSERVED IN A PHASE 3B AND
POST-MARKETING OBSERVATIONAL STUDY
G. Burmester1, X. Mariette2, F. Navarro-Blasco3, U. Oezer4, S. Kary4,
K. Unnebrink4 and H. Kupper4
1
Rheumatology and Clinical Immunology, Charite´ - University
Medicine, Berlin, Germany; 2Department of Rheumatology,
Universite´ Paris-Sud Hoˆpital Biceˆtre, Le Kremlin Biceˆtre, France;
3
Department of Rheumatology, Hospital General, Universitario de
Elche, Alicante, Spain; 4GPRD, Abbott GmbH & Co. KG,
Ludwigshafen, Germany
Background: In the phase 3b ReAct study, adalimumab (ADA) was
added to inadequate DMARD therapy in patients (pts) with longstanding, active rheumatoid arthritis (RA). ReAlise evaluated the longterm safety and effectiveness of ADA in pts who completed ReAct.
This analysis examined long-term safety and effectiveness from the
first injection in ReAct until the last observation (LO) in ReAlise.
Methods: Pts who completed ReAct within 12 months were eligible to
enroll in ReAlise. Adverse events (AEs) were tabulated by 5 time
windows after the first ADA injection. Standardized Mortality Rates
(SMR) and Standardized Incidence Ratios (SIR) for malignancies were
calculated. For SIR, study results were compared with the NCI SEER
database. For SMR, study results were compared to an age- and sexmatched European cohort (WHO statistics, 2001). Effectiveness
measures (observed values) included % of pts with low disease
activity (LDA) or remission (REM), by SDAI 11 and 3.3, respectively,
at 0.5, 1, 3, and 5 yrs and at LO after the first ADA injection.
Results: Among pts from ReAct, 52% (3435/6610) enrolled in ReAlise.
In ReAct, baseline median age, DAS28, and HAQ-DI were 55 yrs, 6.1,
and 1.73, respectively. The median (range) treatment duration was
2045 (129–2681) days (5.7 yrs). The SIR (95% CI) was 0.64 (0.53–0.76)
for all malignancies, and 1.99 (1.11–3.28) for lymphomas. The SMR
was 0.71 (0.57-0.87). Table 1 shows AEs over time. The percent of
patients with LDA and REM at LO were 50% and 21%, respectively.
Conclusions: Long-term data are subject to positive selection bias.
However, in a trial representing routine clinical practice, no new safety
concerns were observed during a median follow-up of > 5 yrs of ADA
treatment (about 20,000 PYs). Effectiveness of ADA was maintained
during long-term observation.
Disclosure statement: G.B. received research grants and consultancy fees or other remuneration from, and is a member of the
speakers bureau of, Abbott. S.K. received consultancy fees or other
remuneration from Abbott. H.K. is an employee of, and possible stock/
option holder in, Abbott. X.M. received research grants from Pfizer and
Roche, and consultancy fees or other remuneration from
GlaxoSmithKline, Pfizer, Roche and UCB. F.N. received research
grants from Roche. U.O. is an employee of Abbott. K.U. is an
employee of, and possible stock/option holder in, Abbott. All other
authors have declared no conflicts of interest.
178. RANDOMIZED EFFICACY AND DISCONTINUATION
STUDY OF ETANERCEPT VERSUS ADALIMUMAB (RED SEA):
A PRAGMATIC, OPEN-LABEL, NON-INFERIORITY STUDY OF
FIRST TNF INHIBITOR USE IN RHEUMATOID ARTHRITIS:
1-YEAR DATA
Paresh Jobanputra1,2, Fiona Maggs1, Alison Deeming3,
David Carruthers3, Elizabeth Rankin1,2, Alison Jordan1,2,
Abdul Faizal4, Carolyn Goddard5, Mark Pugh5, Simon Bowman1,2,
Sue Brailsford1 and Peter Nightingale6
1
Department of Rheumatology, Queen Elizabeth Hospital
Birmingham, Birmingham, United Kingdom; 2Infection & Immunity,
University of Birmingham, Birmingham, United Kingdom;
3
Department of Rheumatology, City Hospital, Sandwell & West
Birmingham Hospitals NHS Trust, Birmingham, United Kingdom;
4
Department of Rheumatology, Solihull Hospital, Heart of England
NHS Foundation Trust, Solihull, United Kingdom; 5Department of
Rheumatology, St Mary’s Hospital, Newport, Isle of Wight,
United Kingdom; 6Wellcome Trust Clinical Research Facility, Queen
Elizabeth Hospital Birmingham, Birmingham, United Kingdom
Background: To date no randomized trial has compared two different
TNF inhibitors for RA. Our goal was to compare adalimumab against
etanercept in patients with active RA who had not responded to, or
were unable to tolerate, two disease-modifying anti-rheumatic drugs
including methotrexate (MTX).
Methods: One hundred and twenty five patients who met national
criteria for treatment with a TNF inhibitor in regard to lack of response to
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Methods: We undertook a SLR investigating the relationship between
the use of MTX in patients with RA and VZV & HZ infection in
Cochrane, Medline, EMBASE and Web of Science databases from
1980 onwards. Additionally, the European Centre for Disease
Prevention and Control, Health Protection Agency, the CDC, rheumatology societies and WHO web sites and publications were consulted
for recommendations regarding immunization in immunocompromised
patients.
Results: 35 studies fulfilled the inclusion criteria comprising 6 case
reports and 29 observational studies. Among the case reports, one
reported 2 cases of VZ in patients receiving MTX for RA and the other 5
case studies presented data on complicated HZ. 22 observational
studies directly addressed the issue of an association between low
dose MTX use and increased susceptibility to any infection including
VZV or HZ infection. In addition four studies compared infection rates
on MTX with other widely used RA therapies and three studies
investigated infection in regard to duration of MTX therapy. Ten studies
considered the association between MTX and non-varicella-specific
infection in RA patients; nine of these concluded that the MTX therapy
is not associated with increased susceptibility to infection.
Six case reports and 13 observation studies considered the
association between MTX and HZ. Three of the observational studies
reported a positive association although in 5 cases, patients were
concurrently treated with prednisolone. Two studies reported a HZ
infection rate of 5%; however each of the cohorts only contained 21
patients in total. One study reported a similar HZ infection rate of 7% in
45 patients. Five studies concluded that there was no association
between HZ and MTX. Three studies comparing the infection rates of
MTX with other RA therapies concluded that MTX did not have higher
HZ infection rates. The other three studies examining the association
between duration of MTX treatment and HZ failed to show a link.
Conclusions: No evidence exists to support a link between MTX and
VZV infection in RA patients and the data regarding the role of MTX in
HZ development is conflicting. The role of pre-MTX VZV screening is
controversial and as it may delay RA therapy we suggest avoiding VZV
screening in this context. Future guidelines should clarify whether
screening for VZV immunity prior to treatment is desirable.
Disclosure statement: A.O. has received honoraria from Roche/
Chugai, BMS, Pfizer, MSD, Abbott, Wyeth, Merck Sorono and UCB. All
other authors have declared no conflicts of interest.
POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
179. METHOTREXATE THERAPY, RHEUMATOID ARTHRITIS
AND LIFE-THREATENING LIVER COMPLICATIONS: SHOULD
WE BE MONITORING MORE CLOSELY?
Nicola Tugnet1, Sheldon C. Cooper2 and Karen M. Douglas3
Rheumatology, The Royal Wolverhampton Hospitals NHS Trust,
Wolverhampton, United Kingdom; 2Gastroenterology, Dudley Group
of Hospitals NHS Trust, Dudley, United Kingdom; 3Rheumatology,
Dudley Group of Hospitals NHS Trust, Dudley, United Kingdom
1
Background: Methotrexate (MTX) is first line therapy for rheumatoid
arthritis (RA) worldwide. We present the case of a young woman
with RA who developed life-threatening complications from liver
disease after low-dose exposure to MTX, in the presence of normal
transaminases, which lead to a review of our practice.
Methods: A previously well 26 year old woman with a 4 year history of
RA presented with massive haematemesis. An urgent OGD showed
bleeding oesophageal varices, which were ligated. An USS confirmed
parenchymal liver disease, ascites and portal hypertension, but no
evidence of hepatic or portal vein thromboses, and a normal biliary
system. She was treated with diuretics, beta blockers, terlipressin and
folinic acid rescue therapy, and her condition stabilized.
Results: She had been treated with MTX 20 mg weekly (approximate
cumulative dose of 4 g) but due to disease activity she had
commenced an anti-TNF agent (golimumab), receiving 2 doses prior
to presentation. She had mild asthma, no family history of liver disease
and drank minimal alcohol. Her BMI was 21 kg/m2. Monitoring for MTX
had shown normal transaminases but ALP had been mildly elevated
for 12 months, ranging from 120 to 170 IU/l. A complete screen was
performed to investigate the cause of liver disease (see table). Liver
biopsy revealed dilated sinusoids, suggesting portal hypertension, and
marked fibrosis consistent with early cirrhosis. In the absence of an
alternative cause, MTX was implicated.
Conclusions: Several months after discontinuing MTX, liver synthetic
function has returned to normal and varices were absent on repeat
endoscopic surveillance. The incidence of MTX-induced liver cirrhosis
is rare. Severe hepatic toxicity is usually manifest by persistent
elevation of ALT/AST. In this patient, the only abnormality had been
mild elevation of ALP, which is commonly seen in low-level inflammation due to RA.
Despite receiving only 4 g of MTX, the patient developed silent
cirrhosis and portal hypertension, which became apparent when
hepatic decompensation occurred via bleeding oesaphageal varices.
This case serves as a potent reminder that MTX can cause silent, but
catastrophic, hepatic damage. Neither EULAR nor BSR guidelines
recommend specific regular monitoring of ALP and concentrate on
AST and ALT. Clinicians should also monitor ALP and consider further
investigation where ALP is persistently raised, even if transaminases
are normal.
TABLE 1.
Biochemistry/
Haematology
Result (on
admission)
Viral/Autoimmune/
Biochemical Screen
Results
ALP (40–120) IU/l
ALT (7–56) IU/l
Alb (35–50) (g/l)
Br (3–17) umol/l
Hb (12.0–16.0) g/dl
INR (0.8–1.2)
Plt (140–400) 109/l
MCV (78–98) fl
103
68
21
70
8.4
2.4
144
87
Negative
Weakly positive
Negative
Negative
Negative
Normal
Normal
Negative
Iron studies
Normal
Hepatitis B / C / E
ANA
AMA
SMA
ANCA
Immunoglobulins
Alpha-1-antitrypsin
Antiphospholipid &
thrombophilia screen
24 hr urinary copper
excretion (0–0.9)
umol/24 h
0.44
Disclosure statement: All authors have declared no conflicts of
interest.
180. LEFLUNOMIDE-ASSOCIATED SEVERE DYSLIPIDAEMIA
IN A RHEUMATOID ARTHRITIS PATIENT
Chong Seng Edwin Lim1, Samantha Bee Lian Low2, Clayton Joy1,
Lynne Hill1 and Paul Davies1
1
Rheumatology, Broomfield Hospital, MEHT, Chelmsford,
United Kingdom; 2General Medicine, Queens Hospital, BHRUT,
Romford, United Kingdom
Background: Leflunomide (LEF) is hepatotoxic but its effects on
cholesterol and triglyceride are not well known. There have only been
two documented cases of severe hypertriglyceridaemia with patients
on LEF for rheumatoid arthritis (RA).
Methods: We describe the first published case of severe dyslipidaemia in a RA patient treated with LEF in the UK.
Results: 62 year old gentleman, with no known medical or family
history was diagnosed with RA 13 years ago. He was first treated with
sulfasalazine for 6 months but stopped due to gastrointestinal (GI)
symptoms. He was then started on methotrexate (MTX). This was
stopped after a month, stating similar GI problems and was lost to
follow up.
He re-presented 5 years later after failure of disease control with
diclofenac. He was then treated with intramuscular steroids, celecoxib
and MTX. For the next 2.5 years, there was a difficulty in stabilizing the
MTX dose due to poor patient compliance. After 6 months without
MTX, LEF was tried. Patient tolerated LEF for 7 months without severe
biochemical hepatotoxicity. However, his disease remained poorly
controlled (DAS28 ¼ 6.40, 6.16) and infliximab was offered. Disease
control has since been achieved with infliximab and subcutaneous
MTX.
During LEF therapy, the patient was admitted with chest pain, later
diagnosed as musculoskeletal pain. He was also found to have mild
hypertriglyceridaemia (A, see table). After 2 years of LEF therapy,
TABLE 1.
Dates
8/1/8
30/3/9
15/4/9
3/8/9
4/1/10
Events
Cholesterol (0-5 mmol/L)
Triglyceride (0.3-1.8 mmol/L)
Fasting cholesterol (0-5 mmol/L)
Fasting triglyceride (0.3-1.8 mmol/L)
Fasting glucose (3.6-6.1 mmol/L)
A
4.88
3.65
B
7.78
18.05
C
D
E
7.62
11.42
4.6
9.16
18.07
6.96
16.94
26/3/10
F
17.21
80.14
13/4/10
13/5/10
6/8/10
G
H
I
22.79
102.61
14.53
40.50
7.04
8.29
5.4
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
at least two DMARDs including MTX were randomized to adalimumab
40 mg every other week or etanercept 50 mg weekly subcutaneously.
The primary outcome was continuation with therapy after 52 weeks.
This was a pragmatic randomized (1:1) open-label study designed to
demonstrate that adalimumab was not inferior to etanercept by a
margin of 15% in terms of drug continuation. Treatment allocation was
stratified by baseline MTX use. No constraints were imposed on
changes in the dose of methotrexate, use of other DMARDs,
including those that had not been tried previously, or on use of oral,
parenteral or intra-articular corticosteroids.
Results: Patient characteristics at baseline were similar: overall 88%
of patients were rheumatoid factor or anti-CCP antibody positive and
66.7% of patients took MTX at baseline. After 52 weeks 39 out of 60
(65%) of patients allocated adalimumab were still on treatment
compared with 34/60 (56.7%) allocated etanercept. Five patients
who did not start allocated treatment were excluded from the
analyses. The one-sided 95% confidence interval (CI) for the
proportion still taking adalimumab minus the proportion on etanercept
was -7.9%, demonstrating non-inferiority at the 15% margin. At 52
weeks the proportion of good, moderate and non-responders based
on DAS28-CRP were 26.3%, 33.3%, and 40.4% for adalimumab
versus 16.7%, 31.7%, and 51.7% for etanercept (p ¼ 0.158). Changes
in DAS28(CRP4) from baseline were a mean of 1.54 (standard
deviation (SD) 1.47) for adalimumab compared with 1.34 (SD 1.33)
for etanercept (p ¼ 0.469). The baseline median EQ-5D scores were
0.52 for both groups. After 52 weeks, or on withdrawal, scores were
improved on adalimumab to 0.62 compared with 0.59 for etanercept
(p ¼ 0.015). Global satisfaction, effectiveness, side effects, and
convenience scores based on the Treatment Satisfaction Score
(version 2) at 52 weeks or on withdrawal were 83.3, 66.7, 91.7, 83.3
for adalimumab compared with 75.0, 66.7, 91.7, and 83.3 for
etanercept (p not significant for all domains). Fourteen serious adverse
events occurred including two deaths from myocardial infarction, one
patient who developed ovarian cancer and one with acute myeloid
leukaemia.
Conclusions: Adalimumab and etanercept, when compared on the
basis of drug continuation at 52 weeks and disease activity scores, are
similarly effective in patients with RA not responding favourably to two
or more DMARDs including MTX.
Disclosure statement: All authors have declared no conflicts of
interest.
iii117
iii118
Wednesday 2 May 2012, 10.45 – 11.45
POSTER VIEWING II
during an annual biologics therapy assessment, an abnormal lipid
profile (B, C) was noted. Despite dietary modification and two lipidlowering drug therapies, his lipid measurements worsened (D) and he
was referred to endocrinology. The patient was diagnosed with mixed
dyslipidaemia and ezetimib started which improved his lipid profile
transiently (E). During an annual biologics re-assessment, his lipid
profile had worsened further (F). An urgent fasting lipid profile (G) was
performed and its severity prompted the immediate stoppage of the
3 year long LEF therapy. This intervention led to rapid and consistent
biochemical improvement (H, I). The patient was subsequently
discharged from endocrinology. The case demonstrates LEF-associated dyslipidaemia with lipid normalization achieved on LEF
discontinuation.
Conclusions: During LEF therapy, liver function tests showed mild
transient intermittent fluctuations. Dyslipidaemia was only discovered
during routine lipid screening in this asymptomatic patient. This case
highlights the need for lipid screening in patients on LEF. We advocate
regular lipid screening for at least 2 years to avoid the complications
associated with severe dyslipidaemia.
Disclosure statement: All authors have declared no conflicts of
interest.
Sandeep Mukherjee1, Patricia Cornell1, Sarah L. Westlake1,
Selwyn Richards1, Fouz Rahmeh1 and Paul W. Thompson1
1
Rheumatology, Poole Hospital NHS Foundation Trust, Poole,
United Kingdom
Background: Intensive early management of RA substantially
improves disease activity, progression, physical function and quality
of life. RA patients had been routinely managed within the rheumatology department at our DGH. In March 2010 a monthly review clinic
was instigated for patients with RA of under 2 years duration and for
those with active disease. Monitoring and management at this clinic
was done according to a strict protocol for tight disease control based
partly upon NICE clinical guideline 79 and agreed by all clinicians. No
extra cost was involved as pre-existing clinic slots were freed up by
moving patients with stable disease to annual review while ensuring
access to urgent assessment if needed
Methods: A retrospective audit of management of RA patients in the
monthly review clinics was undertaken to ensure compliance with
NICE guidelines. This also assessed treatment response at 3, 6, 9 and
12 months for 53 patients newly diagnosed with RA since March 2010
based on American College of Rheumatology classification criteria
2010. Patients with Disease Activity Score 28 (DAS28) values less than
2.6 were considered to be in remission while readings between 2.6 and
3.1, between 3.2 and 5.0 and over 5.1 were classified as low,
moderate and severe disease respectively
Results: Demographics of new RA patients were Male:Female ¼ 1:1.4
and mean age:62 years. 66% patients were Rheumatoid factor
positive. 30% of patients were in remission at 3 months which
increased to 47% at 1 year and another 9% had low disease activity.
Number of patients with moderate disease fell from 55% to 30% and
severe disease from 25% to 9% over the 12 months (See Table 1).
96% patients were started on Methotrexate at diagnosis, 25% in
combination with Hydroxychloroquine. 2% of patients were each
started on Sulfasalazine or Hydroxychloroquine as monotherapy. After
3 months all patients were on Methotrexate, with 64% on combination
therapy. At the end of 1 year 96% patients were on Methotrexate while
62% were on combination therapy and all patients with severe disease
activity (9%) had started biologic agents
Conclusions: Protocol driven tight control of RA at our Rheumatology
department resulted in over 50% of new RA patients achieving
remission or low disease activity by the end of 1 year whilst there was
a significant reduction in the number of patients with moderate and
severe disease activity. This was done through implementation of
monthly review clinics and departmentally agreed tight disease control
protocol without any additional cost
TABLE 1 Percentage of total new RA patients with disease activity levels at different
time intervals
Baseline 3 months 6 months 9 months 12 months
Remission
Low disease activity
Moderate disease activity
Severe disease activity
Missing data
9
8
55
25
4
30
9
43
15
2
28
15
32
21
4
38
9
42
9
2
47
9
30
9
4
Disclosure statement: All authors have declared no conflicts of
interest.
Ferdinand Breedveld1, Edward Keystone2, Desiree van der Heijde1,
Robert Landewe´3, Josef S. Smolen4, Benoıˆt Gue´rette5,
Melissa McIlraith5, Hartmut Kupper6, Shufang Liu7 and
Arthur Kavanaugh8
1
Department of Rheumatology, Leiden University Medical Center,
Leiden, Netherlands; 2Department of Rheumatology, University of
Toronto, Toronto, Ontario, Canada; 3Department of Rheumatology,
Academic Medical Center, Amsterdam, Netherlands; 4Department of
Rheumatology, Medical University of Vienna, Vienna, Austria;
5
GPRD, Abbott, Rungis, France; 6GPRD, Abbott GmbH & Co. KG,
Ludwigshafen, Germany; 7Abbott, Abbott Park, Illinois, United States
of America; 8Department of Rheumatology, University of California at
San Diego, La Jolla, California, United States of America
Background: PREMIER was a phase 3, randomized, controlled trial
(RCT) in MTX-naı¨ve, early RA patients who received blinded
methotrexate (MTX), adalimumab (ADA), or ADA þ MTX for 2 years.
PREMIER demonstrated radiographic, clinical, and functional superiority of initial combination therapy over monotherapies; results were
extended through 5 years, including 3 years open-label (OL) treatment.
This analysis evaluated long-term outcomes in patients treated with
ADA MTX for up to 8 years (6 years beyond the 2-year RCT).
Methods: Patients completing the RCT were eligible to receive OL
ADA for a total of 10 years (trial ongoing); MTX could be added at
investigator’s discretion during OL. This post hoc analysis evaluated
the 8-year-completers cohort with radiographic data available at
baseline (BL) and year 8; results are summarized overall and by initial
treatment arms. Radiographic damage [mTSS, sum of joint-erosion
(JE) and joint-space-narrowing (JSN)] was assessed at BL and years 2,
6, and 8; progressors were defined as change () in mTSS from
BL > 0.5. Differences in mTSS were assessed using longitudinal
ANCOVA following adjustment for BL mTSS. Clinical outcomes
assessed were DAS28, SJC66, and TJC68. Function was assessed
using HAQ-DI.
Results: 299 of 799 randomized patients (37.4%; 103/96/100 from
initial ADA þ MTX/MTX/ADA arms, respectively) received OL
ADA MTX through year 8. Through 8 years of ADA MTX, patients
continued to demonstrate inhibition of radiographic progression and
effective disease control (mean: mTSS ¼ 8.6, DAS28 ¼ 2.6, HAQDI ¼ 0.6). Approximately half of patients experienced absence of
swollen (52.5%) and tender (47.9%) joints. Initial randomization to
ADA þ MTX resulted in lower mean mTSS, JE, and JSN at year 8
(3.8, 1.4, 2.4, respectively) compared with either MTX (11.4, 6.1, 5.2) or
ADA (10.8, 5.6, 5.3) monotherapy (P < .001 for both mTSS
comparisons); ADA þ MTX patients had fewer radiographic progressors (56.3% versus 72.9% and 73.0% for MTX/ADA monotherapy,
respectively). OL ADA MTX treatment inhibited radiographic progression in patients initially randomized to MTX or ADA monotherapy
to levels comparable with those during OL treatment of initial
ADA þ MTX patients. Initial randomization to combination therapy
was also associated with greater proportions of patients achieving
high-level disease control and normal physical function at year 8
(DAS28 < 2.6: 71.3%/58.4%/49.5%, and HAQ-DI < 0.5: 60.2%/
55.9%/47.4%, for ADA þ MTX/MTX/ADA, respectively).
Conclusions: Through 8 years of ADA MTX treatment, patients with
early, aggressive RA maintained effective disease control. Patients
who initially received ADA þ MTX demonstrated better long-term
outcomes than those initially receiving either monotherapy.
Disclosure statement: F.B. received consultancy fees or other
remuneration from Centocor, Schering-Plough, Amgen/Wyeth and
Abbott. B.G. is an employee of, and possible stock/option holder in,
Abbott. A.K. received consultancy fees or other remuneration from
Abbott. E.K. received research grants from Abbott, Amgen,
AstraZeneca, Bristol-Myers Squibb, Centocor, F Hoffmann-LaRoche,
Genzyme, Merck, Novartis, Pfizer and UCB, consultancy fees or other
remuneration from Abbott, AstraZeneca, Biotest, Bristol-Myers
Squibb, Centocor, F Hoffmann-LaRoche, Genentech, Merck,
Nycomed, Pfizer and UCB, and is a member of the speakers bureaus
of Abbott Laboratories, Bristol-Myers Squibb, F Hoffman-LaRoche,
Merck, Pfizer and UCB. H.K. is an employee of, and possible stock/
option holder in, Abbott. R.L. has received research grants from
Abbott, Centocor, Merck, BMS, Pfizer and UCB, consultancy fees or
other remuneration from Abbott, Centocor, Merck, BMS, Pfizer and
UCB, and is a member of the speakers bureaus of Pfizer and UCB. S.L.
is an employee of, and possible stock/option holder in, Abbott. M.M. is
an employee of, and possible stock/option holder in, Abbott. J.S. is
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
181. TIGHT CONTROL OF RHEUMATOID ARTHRITIS IN
PRACTICE AT A DISTRICT GENERAL HOSPITAL THROUGH
MONTHLY REVIEW AT NO ADDITIONAL COST
182. INITIAL COMBINATION THERAPY WITH ADALIMUMAB
PLUS METHOTREXATE LEADS TO BETTER LONG-TERM
OUTCOMES THAN WITH EITHER MONOTHERAPY IN
PATIENTS WITH EARLY RHEUMATOID ARTHRITIS: 8-YEAR
RESULTS OF AN OPEN-LABEL EXTENSION OF A PHASE 3
TRIAL
POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
an employee of, and possible stock/option holder in, Abbott. D.V.
has received research grants from Abbott, Amgen, AstraZeneca,
BMS, Centocor, Chugai, Eli Lilly, GSK, Merck, Novartis, Otsuka,
Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB and Wyeth, and
consultancy fees or other remuneration from Abbott, Amgen,
AstraZeneca, BMS, Centocor, Chugai, Eli-Lilly, GSK, Merck,
Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough,
UCB and Wyeth.
183. CASE SERIES OF TUBERCULOSIS IN ANTI-TNF
THERAPY
1
iii119
1. Focus screening on TB rates in country of birth, TB contact and
travel to endemic areas.
2. IGRA, less attenuated by immunosuppression.
3. First-line treatment with ETA for any at risk patient.
4. If using Mab, lower threshold for TB prophylaxis.
5. During therapy: education re TB symptoms, CXR and IGRAs.
Disclosure statement: All authors have declared no conflicts of
interest.
184. LATE ONSET NEUTROPENIA IN RHEUMATOID
ARTHRITIS TREATED WITH B-CELL DEPLETION
1
Rachel Byng-Maddick and Henry Penn
1
Rheumatology, Northwick Park Hospital, Harrow, United Kingdom
Background: Late onset neutropenia (LON) secondary to rituximab
(RTX) was thought to be exclusive to patients with haematological
conditions. Recently there have been reports of LON complicating RTX
treatment for rheumatological indications. Our aim was to identify the
occurrence of LON following RTX therapy for rheumatoid arthritis (RA).
Methods: We retrospectively reviewed all patients with RA treated
with RTX between October 2007 and July 2011 using the day unit
database, case notes, clinic letters and pathology system. We defined
neutropenia as a neutrophil count < 1.5 109/l occurring at least 4
weeks after RTX, for which no other cause was identified. Patients with
pre-treatment neutropenia were excluded. For each patient we
recorded demographics, serology, concurrent DMARDs, number of
cycles of RTX, neutrophil count pre treatment and up to one year after
the last cycle. RTX regime was 1 g IV given 2 weeks apart. This was
repeated as clinically needed but no less than 6 monthly. FBC was
monitored according to DMARD guidelines or 3 monthly, or at the time
of clinical review.
Results: We identified 111 patients treated with RTX for RA (72%
women). Median age 64 years (23–86). 73 patients were sero-positive
for RF or CCP (10 negative, 28 unrecorded). 68 patients (61%) were on
DMARDs. Patients received up to 8 cycles of RTX, median 2. A total of
265 cycles were given.
5 patients (4.5%) had LON after a mean of 142 days. LON occurred
after 1.9% of cycles. 2 were on MTX, one on MMF. DMARD dose was
stable and there had been no previous neutropenia. 2 were not taking
DMARDs. 2 had neutropenic sepsis with pneumonia. Granulocyte
colony stimulating factor (G-CSF) was given to 2 patients - 1 sepsis,
1 recent joint replacement (patient 2). The maximum duration of
neutropenia was 15 days.
There was no recurrence of neutropenia in 2 patients who were
retreated with RTX (follow up > 6 months).
(Table 1)
Conclusions: LON occurred in up to 4.5% of our RA patients and after
1.9% of RTX treatment cycles. LON may be profound, occurring
several months after RTX therapy, and can be associated with
infection. We may have underestimated the frequency of LON as we
did not routinely check FBC after RTX except in patients on DMARDs.
Although repeated RTX cycles have been a suggested risk factor for
LON, it can occur after just one cycle. It is therefore imperative that we
are aware of LON and monitor FBC; the frequency of monitoring is
uncertain as LON is transient.
Disclosure statement: R.W. has received consultancy fees from
Roche. All other authors have declared no conflicts of interest.
TABLE 1.
No
Age at
first
RTX(y)
Sex
Disease
duration when
RTX started (y)
DMARDs
Total no.
of RTX
cycles
No. of RTX
cycles before
neutropenia
Absolute
neutrophil
count nadir
(x109/l)
Interval between
RTX and
neutropenia (d)
Duration of
neutropenia
(d)
G-CSF
Complications
1
2
3
4
5
63
25
62
51
55
F
F
F
M
F
18
10
14
24
19
None
None
MMF
MTX
MTX
1
7
5
2
2
1
7
3
1
1b
0
0
0
0.4
1.3
168
71,106
151
184
135
9
14,4a
7
15
14
no
yes
yes
no
no
Sepsis(chest)
no
Sepsis(chest)
no
no
a
Patient 2 had a spontaneous recovery from an initial period of asymptomatic neutropenia, but this recurred 21 days later. bFollow up 1 month after retreatment.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: It is widely reported that anti-TNF therapy increases the
risk of reactivation of Mycobacterium tuberculosis (MTB). Risk is
higher with monoclonal antibodies (Mab), rather than etanercept (ETA),
and continues after stopping treatment.
Our hospital is based in an endemic area for MTB. Incidence rates
reached 122 per 100000 in 2010. Despite the BTS screening
programme to detect latent TB infection prior to anti-TNF therapy,
we have had 5 cases of active TB.
Methods: Notes from all patients ever registered on the hospital’s
drug monitoring system for anti-TNF therapy were scrutinized for data
regarding TB screening. London TB registry confirmed diagnoses of
active TB.
Results: 5 cases of TB were identified from 382 on anti-TNF therapy
over 10 years:
Case 1:68 yr old Caucasian female with rheumatoid arthritis (RA),
on adalimumab (ADA) for 15 months. At screening she had a negative
Mantoux (on immunosuppression), normal chest radiograph (CXR), no
TB history, but her brother had had TB. She developed pulmonary TB
with new radiographic changes and responded well to anti-TB therapy.
Case 2:68yr old Caucasian female with RA, on ADA for 15 months.
At screening she had a negative Mantoux (on immunosuppression),
normal CXR, no personal TB history, but had contact with TB in a
family member > 20 years ago. She developed pulmonary TB and
responded well to anti-TB therapy.
Case 3: 47yr old Asian male born in India, living in UK for 22 years.
He had ankylosing spondylitis, on ADA for 3 years. At screening he had
a negative Mantoux (not immunosuppressed), normal CXR and no
history or contact with TB. He developed miliary TB and required
9 months treatment.
Case 4:49yr old Caucasian female with psoriatic arthritis and
crohn’s disease on ADA for 14 months. Screening revealed negative
Mantoux, normal CXR, no personal TB history or contact. She
developed miliary TB and granulomatous hepatitis and needed
9 months treatment.
Case 5:57yr old Asian female born in Pakistan. At screening she
had a Grade II Heaf test (on methotrexate and steroids) and normal
CXR. Within 3 months of Infliximab for RA, she developed TB
lymphadenitis. She recovered after 6 months treatment.
Conclusions: This audit shows the screening process is unable to
exclude TB risk, and has not reduced TB compared to rates expected
from pre-screening era data.
All cases occurred on Mab therapy, despite 47.9% treated with
ETA. This concurs with previous data showing increased risk with ADA
v ETA (144 v 39/100000 person yrs respectively).
According to 2005 BTS guidelines, 80% were low risk, although
75% these had TB contact. These cases developed infection >1 year
on therapy.
The current screening process is inadequate. New guidelines are
required:
Rita Abdulkader1, Chethana Dharmapalaiah1, L. Shand1,
Ginny Rose1, Gavin Clunie1 and Richard Watts1
1
Rheumatology Department, The Ipswich hospital NHS Trust,
Ipswich, United Kingdom
iii120
Wednesday 2 May 2012, 10.45 – 11.45
POSTER VIEWING II
185. ARE PATIENTS WITH LONG-STANDING RHEUMATOID
ARTHRITIS TREATED-TO-TARGET? AN AUDIT OF
FOLLOW-UP PATIENTS IN RHEUMATOLOGY CLINIC
Amr Eldashan1, Bhaskar Dasgupta1 and Frances A. Borg1
1
Rheumatology, Southend Hospital, Westcliff-on-Sea,
United Kingdom
TABLE 1.
Monotherapy (%)
Combination (%)
Biologics (%)
DAS < 3.2
DAS 3.2-5.1
DAS > 5.1
Not recorded
35
39
53
40
35
26
16
26
16
9
0
5
Disclosure statement: All authors have declared no conflicts of
interest.
186. AUTOLOGOUS TOLEROGENIC DENDRITIC CELLS
IN RHEUMATOID ARTHRITIS
Gillian M. Bell1,2, Amy E. Anderson1, Rachel A. Harry1,
Jeroen N. Stoop1, Catharien M. Hilkens1, John Isaacs1,2,
Anne Dickinson3 and Elaine McColl4
1
Musculoskeletal Research Group, Newcastle University, Newcastle
upon Tyne, United Kingdom; 2Musculoskeletal Unit, Freeman
Hospital, Newcastle upon Tyne, United Kingdom; 3Haematological
Sciences, Newcastle University, Newcastle upon Tyne,
United Kingdom; 4Clinical Trials Unit, Newcastle University,
Newcastle upon Tyne, United Kingdom
Background: Due to constraints in current RA therapies e.g. nonspecific immunosuppression, it is desirable to develop therapeutic
agents which specifically target auto-reactive T cell responses.
In health, dendritic cells maintain tolerance to self antigens but also
direct pathological immune responses in autoimmunity. Our hypothesis is that it is feasible to make immunomodulatory dendritic cells
(tolerogenic dendritic cells or tolDC) from human peripheral blood and
use these cells to restore self-tolerance and thus down- regulates the
autoaggressive response in RA.
Methods: Pharmacological reagents (dexamethasone and vitamin D3)
were used to modify the differentiation of human blood monocytes and
murine bone marrow cells into tolDC. Human tolDC were characterized
by phenotype, cytokine production and functional effects on cocultured T-cells. The therapeutic properties of murine tolDC were
assessed in collagen-induced arthritis. We subsequently developed a
protocol for producing human tolDC under GMP conditions (GMP
tolDC), with a view to conducting a phase I study.
Results: TolDC present antigen but have a reduced co-stimulatory
capacity and an anti-inflammatory cytokine profile. They express
CCR7 and migrate towards CCL19. Co-culture of tolDC with T-cells
leads to imprinting of an anti-inflammatory phenotype (naive T-cells) or
an anergic phenotype (memory T-cells). In collagen-induced arthritis,
tolDC potently suppress established synovitis. They home to the sites
of inflammation, and skew the immune response from IL-17 to IL10
production. GMP tolDC are highly stable and refractory to stimulation
by TLR ligands or proinflammatory cytokines. During differentiation
they are loaded with autologous synovial fluid as a source of
autoantigen. We have now received regulatory approvals to commence a phase I study of tolDC in patients with RA. GMP tolDC will be
administered intra-articularly (via arthroscopy) to patients with an
inflamed knee joint, permitting synovial biopsy pre- and post-therapy
187. TUBERCULOSIS (TB) PROPHYLAXIS BEFORE
ANTI-TNF-a: BTS VERSUS T SPOT
Snehashish Banik1, Lorna Smith2, Janice France1 and
Sandeep Bawa1
1
Rheumatology, Gartnavel General Hospital, Glasgow,
United Kingdom; 2School of Medicine, Glasgow University, Glasgow,
United Kingdom
Background: Flare of latent TB is a concern for rheumatology patients
who are initiated on anti-TNF-a therapy. There is fivefold increased risk
of TB with anti-TNF-a. Hepatotoxicity with anti-TB medication is also a
worry. There is extensive disparity in screening methods for TB
throughout rheumatology centres in the UK. Most rheumatology
patients are on immunosuppressants. Therefore, Mantoux Test (MT)
is not a sensitive test. T-SPOT, however, is described to have a
sensitivity of 97.2%. For evaluation of patients with a normal chest
radiograph (CXR), BTS guideline recommends to weigh the risk of
hepatitis over the benefits of TB prophylaxis. BTS however does not
incorporate T SPOT testing. We did a study to see whether routinely
performing T-SPOT tests are placing patients at a theoretical risk of
getting drug induced hepatitis.
Methods: We performed a prospective observational study on 100
patients who were investigated for TB prior to commencing anti-TNF-a
therapy at Gartnavel General Hospital in Glasgow. The patients were
seen from February 2010 to March 2011. All patients had risk
stratification in line with the BTS guidelines, with a clinical history,
ethnic origin, place of birth and number of years resident in UK. All
patients had a CXR and T-SPOT.
Results: 94% of the cohort was white British, 3% South Asian, 1%
black African and 2% other ethnic origin. 94% were UK born. 6% were
in UK for more than 5 years. From our cohort no patients had
symptoms of TB nor had a past history of TB. However 3% of these
patients had abnormal CXR, even though their T-SPOTs were
negative. Only 2% had positive T-SPOT. 15% had indeterminate TSPOT result in the first instance, for which they had to have their test
repeated. We then performed an individual risk-benefit calculation as
per BTS guideline. 4 patients qualified for TB Prophylaxis even though
they were T-SPOT negative. They were either South Asian or of black
ethnicity. 2 patients were T-SPOT positive however could have
avoided TB prophylaxis as per BTS guidelines.
Conclusions: Our study is the first to our knowledge to highlight the
limited clinical benefit of T-SPOT to patients about to commence antiTNF-a therapy. Chemoprophylaxis carries a significant risk of drug
induced hepatitis (278–1766 per 100,000) which must be considered
before anti-TB treatment is commenced. An indeterminate T-SPOT
can result delaying the commencement of early treatment with antiTNF-a therapy in a significant number of patients. Each test costs £150
approximately, which occasionally needs repeating with no further
diagnostic gain. Further studies are needed to determine whether
T-SPOT studies are cost effective as a screening tool in adding further
diagnostic and management decisions over current recommendation
of risk stratification by the BTS. The health economics and risk benefit
analysis needs to be addressed to provide clear guidelines for the
rheumatology community.
Disclosure statement: All authors have declared no conflicts of
interest.
188. THE EVALUATION OF MUSCULOSKELETAL
ULTRASOUND IN THE MANAGEMENT OF INFLAMMATORY
ARTHRITIS
Andrew Rutherford1, Ann Scott Russell2, Jacqueline Smith3,
Imad Jassim1, Robin Withrington3, Pauline Bacon4 and
Denise De Lord1
1
Rheumatology, QEQM Hospital, EKHUFT, Margate,
United Kingdom; 2Rheumatology, William Harvey Hospital, EKHUFT,
Ashford, United Kingdom; 3Rheumatology, Kent & Canterbury
Hospital, EKHUFT, Canterbury, United Kingdom; 4Medical Physics,
EKHUFT, Canterbury, United Kingdom
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: Aggressive early treatment is associated with better
outcomes in rheumatoid arthritis. NICE guidelines recommend
combination DMARD therapy. The BSR advises a treat-to-target
approach with escalation of therapy if the DAS score is over 3.2. Much
current research and service planning focuses on early disease. We
explore whether the same approach is seen in patients with longerstanding disease.
Methods: We performed a retrospective casenote audit of consecutive patients with rheumatoid arthritis attending follow-up clinics in
June 2011.
Results: 101 patients were identified; 70 female; mean age 61 years
(range 28-91). 62 had seropositive disease. 31 had radiographic
erosions. 5% had had arthritis for 0-3 months, 3% 3-6 months, 10% 612 months, 12% 1-2 years, 21% 2-5 years, and 49% over 5 years.
Conclusions: Generally the treat-to-target approach was applied to
patients with longer-standing rheumatoid arthritis. Adequate disease
control could be achieved with DMARD monotherapy. 1/3 patients on
combination therapy had active disease, but would not qualify for
biologics under current NICE guidelines. Adequate treatment provision
is needed for this group.
for biomarker assessment at the disease site. Initial results will be
presented at the conference.
Conclusions: We have developed a reliable protocol for the
generation of tolDC from human peripheral blood. Equivalent cells
suppress arthritis in mice and we are about to commence a phase I
study of intra-articular tolDC in RA patients.
Disclosure statement: All authors have declared no conflicts of
interest.
POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
iii121
TABLE 1 Outcome measures at baseline, 12 months and 60 monthsa
DAS28
(mean)
Remission
(DAS28 <2.6) (%)
EULAR good
response (%)
EULAR moderate
response (%)
HAQ (median)
Step-up therapy
Baseline (n ¼ 47)
12 months (n ¼ 44)
60 months (n ¼ 36)
6.9
3.01
3.27
–
48
39
–
64
56
–
27
39
2.125
1.0
1.125
Parallel triple
therapy
Baseline (n ¼ 49)
12 months (n ¼ 47)
60 months (n ¼ 42)
6.75
3.44
3.6
–
34
31
–
43
48
–
47
41
2.0
0.875
1.4375
a
Completer analysis. There were no significant differences in the percentage of responders between the two groups.
189. TRIPLE THERAPY IN EARLY ACTIVE RHEUMATOID
ARTHRITIS: 5-YEAR FOLLOW UP
Laura McGregor1, Islay Morrison1, Anne Stirling2, Duncan R. Porter2
and Sarah A. Saunders1
1
Centre for Rheumatic Diseases, Glasgow Royal Infirmary, Glasgow,
United Kingdom; 2Rheumatology Department, Gartnavel General
Hospital, Glasgow, United Kingdom
Background: We previously reported that within the setting of an
intensive management strategy in early rheumatoid arthritis (RA), stepup disease-modifying (DMARD) therapy was at least as effective as
parallel triple therapy in achieving highly effective control of disease
activity (below). We sought to determine if improvements seen at 12
months were sustained and if there were any differences in outcomes
between the two treatment groups at 5 years.
Methods: The initial trial randomized 96 patients with early RA to
receive step-up DMARD therapy (n ¼ 47) or parallel triple therapy
(n ¼ 49). Both groups had DMARD escalation per protocol within an
intensive management setting treating to a DAS28 target of <3.2. After
completing the 12 month intensive study period the patients returned
to routine rheumatology out-patient care. All patients were invited to
return for study follow up visits 5 years after enrolment. The same
metrologist involved in the original trial performed the clinical
assessments. DAS28 and Health Assessment Questionnaire (HAQ)
scores were measured, and data regarding medication was collected.
Results: 5 year follow up data from 36 patients in the ‘step-up therapy’
group (4 died, 7 lost to follow up) and 42 patients in in the ‘parallel triple
therapy’ group (2 died, 5 lost to follow up) were available for completers analysis. The results are as shown in Table 1. No significant
differences were found between groups. The previously reported nonsignificant trend towards better control in the step-up group persisted.
In the step-up group a similar proportion of patients continued on
monotherapy at 12 months (50%) and at 60 months (47%). Whilst 75%
of patients in the triple therapy group remained on all 3 DMARDs at 12
months, by 60 months this had fallen to 44%.Most patients in the triple
therapy group continued on combination DMARDs with only 12%
receiving monotherapy at 5 years. 6 patients (4 ‘step-up’, 2 ‘triple
therapy’) were on biologic therapies at 5 years.
Conclusions: At 5 years patients treated with a step-up DMARD
strategy continued to do at least as well as those on triple therapy from
the outset with a significant proportion remaining on monotherapy. The
subtantial improvement in disease activity and function seen in both
groups at 12 months was maintained. A small deterioration in mean
DAS28 and median HAQ occurred following transition to routine care.
Disclosure statement: All authors have declared no conflicts of
interest.
Reference
1. Saunders SA, Capell HA et al. Triple therapy in early active
rheumtoid arthritis. A randomized, single blind controlled trial
comparing step up and parallel treatment strategies. Arthritis
Rheum 2008;58:1310–17.
190. AUDIT OF SAFETY AND EFFICACY OF COMBINATION
METHOTREXATE AND LEFLUNOMIDE IN EARLY ARTHRITIS
USING AN ESCALATION STRATEGY
Sara Else1, Olga Semenova1, Helen Thompson1,
Olabambo Ogunbambi1, Sathish Kallankara1, Elaine Baguley1 and
Yusuf Patel1,2
1
Rheumatology, Hull Royal Infirmary, Hull, United Kingdom;
2
Hull York Medical School, Hull, United Kingdom
Background: Recently it has been suggested that combination
leflunomide (LEF) and methotrexate (MTX) (mean MTX dose 14.6 mg/
week) can be effective in treating early rheumatoid arthritis (RA) as well
as established disease [1]. We use a step-up combination strategy in
early RA starting with MTX escalating to 25 mg s/c weekly with
hydroxychloroquine (HCQ) 200 mg daily, followed by addition of LEF
10-20 mg daily. We present our provisional data on the efficacy and
safety of this approach.
Methods: All patients in our early arthritis clinic (EAC) treated with
combination MTX/LEF were audited (disease duration <2 years, age
>18, RA according to ACR/EULAR 2010 criteria). For assessment of
efficacy patients were excluded if they had had DMARDs >3 months
prior to attending EAC. Patients were seen every 4-6 weeks and
treatment escalated if DAS283.2. If RA was still active patients were
then assessed for biologic therapy. We analysed data for safety. We
also assessed efficacy 6 and 12 months post initiation of DMARDs
(DAS28 and EULAR response).
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: NICE guidance for rheumatoid arthritis (RA) approves
the use of ultrasound (US) as a diagnostic tool for the detection of
synovitis and erosions. US use in clinic has been limited due to the
high equipment costs, training requirements and the lack of US tariffs.
However, the benefits of clinician-led US clinics manifestly outweigh
the initial capital expenditure and training costs. US findings taken in
the light of the clinical picture in real-time benefit patients with a
tailored, efficient treatment experience. This streamlined patient
pathway has financial benefits to the commissioner and secondary
care provider alike. EKHUFT is a large multi-site trust serving a
population of 730,000. With the above in mind we recently implemented a CASE-accredited, focussed US course of the hands and feet,
moderated by Canterbury Christchurch University. Training clinics
were set up for the detection of sub-clinical synovitis and erosions. We
aimed to use US observations to improve the patient pathway so that
early clinical decisions could be taken on patient discharge or the
modification of therapy.
Methods: US clinics were performed by 3 consultant rheumatologists
and 1 specialist nurse. Patient groups were targeted as follows: 1)
New and existing patients with an inflammatory history but no obvious
synovitis; 2) Patients with on-going erosive changes and absence of
clinical synovitis; 3) RA patients in clinical remission to detect subclinical synovitis. OMERACT criteria for synovial hypertrophy and
neovascularity were employed for the classification of active ongoing
synovitis.
Results: 122 patients met the inclusion criteria (RA ¼ 69; OA ¼ 20;
UIA ¼ 5; Psoriatic arthritis ¼ 3, Fibromyalgia ¼ 2; tenosynovitis ¼ 8;
hypermobility ¼ 5; other ¼ 10). Of these 32 (26%) were discharged on
the basis of their ultrasound scans (17 discharged immediately and 15
after follow-up to explain their diagnosis and management). 20
patients (17%) were initiated on DMARD therapy and a further 20
(16.5%) had DMARD/Biologic therapy escalated due to their US
findings. Two patients were escalated from anti-TNF to Rituximab
treatment due to US-detected active synovitis. US facilitated a
reduction in DMARD therapy in 6 cases (5%).
Conclusions: The rheumatologist centred approach to US examinations in clinic has clear benefits. Patients with suspected inflammatory
arthropathies (IA), gain from early intervention with DMARDs, minimizing joint damage and those patients with RA in clinical remission, but
with active sub-clinical synovitis, benefit from escalation of their
therapeutic regime, including the use of biologics. Rapid diagnosis and
management of those patients with non-IA arthropathies allows a
reduction in the delay and costs caused by follow-up and further
investigation. At EKHUFT we are initiating one stop clinics with the
utilization of ultrasound for the management of new patients with IA.
Disclosure statement: P.B. received a sessional support grant from
Pfizer and an equipment grant from Abbott. D.D. received a sessional
support grant from Pfizer and an equipment grant from Abbott. I.J.
received a training grant from Pfizer and an equipment grant from
Abbott. A.R. received a training grant from Pfizer. A.S. received a
sessional support grant from Pfizer and an equipment grant from
Abbott. J.S. received a training grant from Pfizer. All other authors
have declared no conflicts of interest.
iii122
Wednesday 2 May 2012, 10.45 – 11.45
POSTER VIEWING II
TABLE 1 Response rates and side-effects with combination MTX/HCQ/LEF
Mean drug doses
EULAR response (%)a
Disease activity (%)
MTX (weekly)
HCQ (daily)
LEF (daily)
Remission
(DAS < 2.6)
Low
(DAS 2.6-3.2)
Moderate
(DAS > 3.2-5.1)
Severe
(DAS > 5.1)
None
Moderate
Good
6 months (n ¼ 10)
12 months (n ¼ 8)
Side-effectsb
24
23.8
200
200
11
13.8
20
75
0
12.5
70
12.5%
0
0
20
12.5
30
25
Age
Sex
MTX (mg)
LEF (mg)
Weeks on current
treatment
Side-effect
Action
63
68
41
51
48
59
62
88
59
50
59
M
M
F
F
F
M
F
F
F
F
F
25
25
25
25
25
25
25
25
20
25
25
10
10
10
20
20
10
20
20
20
20
20
1
1
9
10
6
26
9
<6
21
27
<8
Rash
Diarrhoea
Hypertension
Cytopenia
Diarrhoea
ALT 109 iu/l
ALT 95 iu/l
Pancytopenia
Stomach upset
Cytopenia
Infection
Stopped LEF
Stopped LEF
Stopped LEF
Stopped LEF and MTX
Stopped LEF and MTX
Stopped LEF, reduced MTX to 20 mg
Stopped LEF and MTX
Stopped LEF, reduced MTX to 15 mg
Reduced LEF to 10 mg
Reduced LEF to 10 mg
Temporarily stopped LEF and MTX
a
10
37.5
Data available for 6 of 10 patients at 6 months and 6 of 8 patients at 12 months; ball patients were also on HCQ 200 mg daily.
Reference
1. Sakellariou GT, Sayegh FE et al. Efficacy of leflunomide addition
in relation to prognostic factors for patients with active early
rheumatoid arthritis failing to methotrexate in daily practice. Clin
Rheumatol 2011 Sep 9. [Epub ahead of print].
191. INCOMPLETE RESPONSE OF INFLAMMATORY
ARTHRITIS TO TNFa BLOCKADE IS ASSOCIATED WITH
THE TH17 PATHWAY
Methods: A longitudinal study of two independent cohorts (C1, n ¼ 24.
C2, n ¼ 19) of RA patients treated with anti-TNFa biologics was carried
out to assess changes in their Th17/IL-17 levels before and at 4 and
then 8-12 weeks after commencing anti-TNFa therapy. IL-12/23p40
production was assessed in serum, PBLs and monocytes of patients.
Mice with CIA were treated with anti-TNFa alone, anti-IL17 alone or the
combination of anti-TNFa and anti-IL17. Efficacy of treatment and
response was assessed by changes in DAS-28 ESR scores in patients,
and by clinical scores and histological analysis in CIA. Cells from the
site of inflammation or the periphery of mice with CIA were isolated to
determine the effect of therapy on T cells and associated cytokines.
Results: A significant expansion of Th17 cells was detected in patients
after anti-TNFa therapy and this was accompanied by increased
expression of IL-12/23p40. There was an inverse relationship between
baseline Th17 levels before the initiation of therapy, and the response
of RA patients to anti-TNFa. Additionally, PBLs from non-responder
patients showed evidence of increased p40 and IL-17 production
which translated to a strong correlation between IL-17 levels and the
clinical score of anti-TNFa treated mice. It was also shown that the
combination blockade of TNFa and IL-17 in CIA is more effective than
monotherapy, particularly with respect to the duration of therapeutic
effect.
Conclusions: We conclude that the increase in IL-17/Th17 cells after
TNF blockade may contribute to the lack of response to TNF or to the
frequency of disease flares that occur during therapy or after treatment
is withdrawn. Finally, the efficacy of combination blockade of TNFa
and IL-17 in CIA argues in favour of an IL-17 targeted therapeutic
approach for anti-TNFa non-responder patients and for the evaluation
of combination therapy in RA, provided that safety concerns can be
addressed.
Disclosure statement: All authors have declared no conflicts of
interest.
Saba Alzabin1, Sonya Abraham2, Taher E. Taher3,
Andrew Palfeeman1, Dobrina Hull1, Kay McNamee1, Ali Jawad3,
Ejaz Pathan1, Anne Kinderlerer4, Peter Taylor1, Richard O. Williams1
and Rizgar A. Mageed3
1
Kennedy Institute of Rheumatology, University of Oxford,
United Kingdom; 2Division of Immunology and Inflammation, Imperial
College London, London, United Kingdom; 3William Harvey
Research Institute, Queen Mary University of London, London,
United Kingdom; 4St Mary’s Hospital, Imperial College NHS trust,
London, United Kingdom
Oleg Iaremenko1 and Ganna Mikitenko1
Department of Internal Medicine, National Medical University
O.O.Bogomolets, Kyiv, Ukraine
Background: TNFa antagonists represent a major breakthrough in the
treatment of a number of autoimmune and inflammatory diseases such
as Rheumatoid Arthritis (RA), however, there are obstacles to their
more general use such as the lack of durable therapeutic effect, sideeffects, and variable response levels. We have previously reported that
TNFa blockade in murine collagen-induced arthritis (CIA) resulted in an
elevation of IL-23/IL-12p40 leading to a paradoxical increase in
pathogenic Th17 cells. The aim of this study is to establish if
comparable changes in Th1/Th17 cell populations found in experimental arthritis occur in RA patients treated with anti-TNFa agents,
and whether the therapeutic response to anti-TNFa is compromised in
patients and mice due to elevated Th17/IL-17 levels. Finally, to assess
the efficacy of combined blockade of anti-TNFa and anti-IL-17 in
arthritis.
Background: The optimal result in treatment of patients (pts) with RA
is a combination of good clinical response and slowing/stopping of
joints destruction. The aim of our study is to assess effect of different
nonbiological DMARDs on radiographic progression depending on the
RA duration.
Methods: 133 pts with RA (59.4% with early RA, including 15.8% pts
with very early RA) were studied. Mean age pts was 49.6 0.58 yrs,
mean disease duration - 52.3 3.15 months. 84.2% pts were women,
63.2% - positive for RF and 75.2% - for anti-CCP. Pts were treated
with methotrexate (MTX, 11.6 0.29 mg/w, n ¼ 52), leflunomide (LF,
19.2 0.28 mg/d, n ¼ 25), sulfasalazine (SS, 2 g/d, n ¼ 27) or combined
basic therapy (CBT, n ¼ 29). Effects on radiologic progression after 2
yrs of DMARD treatment by the modified Sharp-van der Heijde score
(SHS) were evaluated.
192. EFFECTS OF DIFFERENT NONBIOLOGIC DISEASEMODIFYING ANTIRHEUMATIC DRUGS ON RADIOGRAPHIC
PROGRESSION OF RHEUMATOID ARTHRITIS DEPENDING
ON DISEASE DURATION (RESULTS OF 2 YEARS OF
MONITORING)
1
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Results: 31 of 105 patients attending EAC had combination MTX/
HCQ/LEF. Mean age 60 years (range 35-88), F:M ratio 1.8:1, mean
disease duration 12 months (range 3-24). 26/31 (84%) were CCP or RF
positive and 6 (19%) had erosions at baseline. Mean DAS28 at initial
assessment was 5.08 (range 3-6.9).
11 of the 31 patients (35%) had side-effects (table 1). Of these
8 (26%) stopped LEF (with 3 also stopping MTX), 2 had dose reduction
LEF and 1 was able to continue with treatment. In all cases sideeffects resolved with treatment withdrawal.
10 patients were on MTX/HCQ/LEF at month 6, mean treatment
time 7.5 weeks (range 1-17). At this point only 20% had DAS 3.2,
however at 12 months, 87.5% had DAS 3.2 (8 patients, mean
treatment time 27 weeks (range 11-42)).
Conclusions: Although the data is limited, escalation therapy with
MTX/HCQ/LEF appears to be safe. It is also effective in treating early
arthritis with 7 out of 8 (87.5%) patients achieving low disease activity
by 12 months with 6 (75%) of these being in remission. More extensive
real-life experience is needed into using this combination of therapies.
Disclosure statement: All authors have declared no conflicts of
interest.
POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
TABLE 1 Dynamics of X-ray changes after 2 yrs of DMARD treatment depending on
RA duration (SHS)
RA duration
MTX
LF
SS
CBT
Very early
Early
Late
4.67 2.20
8.32 1.57
11.5 2.46**
4.0 2.32
5.8 1.60
6.23 1.26*
6.0 3.14
8.5 1.72
11.3 3.03
3.86 2.88
5.4 1.79
7.11 3.49*
*p < 0.05 vs MTX and SS; **p < 0.05 vs very early RA.
Disclosure statement: All authors have declared no conflicts of
interest.
193. DEVELOPMENT OF A NOVEL RECOMBINANT
BIOTHERAPEUTIC WITH APPLICATIONS IN TARGETED
THERAPY OF HUMAN ARTHRITIS
Mathieu Ferrari1, Tahereh Kamalati1 and Costantino Pitzalis1
1
Experimental Medicine and Rheumatology, Queen Mary University
London, London, United Kingdom
Background: It is well established that neovasculogenesis plays a vital
role in the progression and perpetuation of rheumatoid arthritis
(RA), providing nutrients and oxygen to the proliferating synovial
membrane and conveying inflammatory cells to the site of inflammation. Moreover, significant evidence has demonstrated molecular
heterogeneity within the endothelium of different tissues, conferring
organ tropism to migrating lymphocytes subsets by direct interaction
with specific homing receptors. The heterogeneity of the synovial
microvascular endothelium (MVE) can be exploited for the development of organ-specific therapeutic and diagnostic reagents.
Methods: A scFv (scFv A7) antibody with specificity for synovial
arthritic MVE has been isolated following an in vivo phage display
selection on SCID mice double grafted with human osteo-arthritic
(OA) synovium and normal human skin. The reactivity in frozen,
paraffin embedded tissue sections and in cell lines was investigated
using immunohistochemistry and immunofluorescence analysis.
Cytoplasmic and membrane bound proteins from cell lines were
extracted using a multi detergent approach and the presence of scFv
A7 target antigen was assessed through immuno-precipitation and
western blotting analysis.
Results: We have isolated using phage display in double transplanted
SCID mice with human OA synovium and human skin, a human
recombinant antibody, scFv A7, that shows a strong and specific
reactivity with the perivascular cells within the neovasculature of
human RA and OA synovium. scFv A7 shows no detectable reactivity
with the microvasculature or cellular components of a broad spectrum
of tissues derived from normal human organs. In addition no reactivity
could be detected in other inflammatory disease conditions. The scFv
A7 clone proved to efficiently and preferentially target human synovial
microvasculature in xenografts when administered intravenously in
SCID mice.
Conclusions: Our results demonstrate that the reactivity of scFv A7 is
specific to the microvasculature of human arthritic synovium. This
specific reactivity suggests that the target molecule for scFv A7 may
have potential as a biomarker in arthritis and also have applications as
an immunotherapeutic target in the development of new strategies for
therapy of this condition.
Disclosure statement: All authors have declared no conflicts of
interest.
194. TO WHAT EXTENT IS THE NICE GUIDANCE ON THE
MANAGEMENT OF RHEUMATOID ARTHRITIS IN ADULTS
BEING IMPLEMENTED? REGIONAL AUDIT OF THE MIDLANDS
Nicola Tugnet1, Fiona Pearce2, Sofia Tosounidou3,
Karen Obrenovic4, Nicola Erb4, Jonathan Packham5 and
Ravinder Sandhu4
1
Rheumatology, The Royal Wolverhampton Hospitals NHS Trust,
Wolverhampton, United Kingdom; 2Rheumatology, Nottingham
University Hospitals NHS Trust, Nottingham, United Kingdom;
3
Rheumatology, Sandwell & West Birmingham Hospitals NHS Trust,
Birmingham, United Kingdom; 4Rheumatology, Dudley Group NHS
Foundation Trust, Dudley, United Kingdom; 5Rheumatology,
University Hospital of North Staffordshire NHS Trust, Stoke on Trent,
United Kingdom
Background: Rheumatoid arthritis (RA) is a chronic disease associated with significant morbidity. The 2009 NICE guideline gives best
practice advice on the care of adults with early RA. It suggests use of
combination treatment, short-term glucocorticoids and monthly
monitoring of DAS28, until the desired level of control is achieved.
The aim of this regional audit was to assess implementation of the
NICE guidance into clinical practice across the Midlands.
Methods: 19 rheumatology units across the East and West Midlands
participated. 9 units have designated early inflammatory arthritis
clinics (EIAC). Data for all patients diagnosed with definite or probable
RA since February 2009 was prospectively collected over a 2-week
period during 2011, using an audit proforma developed in accordance
with the NICE guideline audit tool.
Results: Data was collected from a total of 311 patients. 81.4% had
definite RA. Mean time from symptom onset to first rheumatology visit
was 25.5 month. However, 76.8% patients were seen in rheumatology
clinic within 3-6 weeks from time of referral.
Rheumatoid factor (RF) was checked in 95.7% of cases of which
69.2% were RF þ . Anti-citrullinated protein antibody (ACPA) was
checked in 81.5% of RFþ patients, of which 72.5% were also ACPAþ.
75.9% of EIAC documented the presence of erosions on X-rays of
hands and feet versus 49.4% of non-EIAC.
In EIAC, 57.9% patients were offered combination therapy versus
30.4% in non-EIAC. Interestingly, combination therapy use varied
between units from 0% - 100%. Units in the West Midlands were more
likely to offer combination therapy.
Methotrexate (MTX) and Hydroxychloroquine was the preferred
combination treatment. MTX was offered in 94.5% of combination
therapy and glucocorticoids were given in 77.9%, with intramuscular
route most popular. Baseline CRP was checked in 98.7% patients but
only 61.3% had monthly CRP. Baseline DAS28 was performed in
60.5% with EIAC performing more monthly assessments than nonEIAC (51.1% vs. 25.4%). 98% patients had a named MDT member
and 80.5% patients had information on RA management.
Conclusions: There is a significant delay between symptom onset and
specialist assessment. However, 95.6% patients are seen within 12
weeks of GP referral. ACPA is commonly checked in RF þ patients.
Units with EIAC are more likely to record the presence of erosions,
offer combination therapy and to assess RA disease activity monthly.
Disclosure statement: All authors have declared no conflicts of
interest.
195. IMMUNOGLOBULIN MONITORING IN PATIENTS WITH
RHEUMATOID ARTHRITIS TREATED WITH RITUXIMAB
Catherine White1, Caroline M. Cardy1, Elizabeth Justice1,
Madeline Frank1 and Lisa Li1
1
Department of Rheumatology, Queen Elizabeth Hospital
Birmingham, Birmingham, United Kingdom
Background: According to NICE Guidelines 2010 the use of Rituximab
in combination with Methotrexate is indicated for adult patients with
severe rheumatoid arthritis (RA) who are intolerant to or have had an
inadequate response to other disease-modifying anti-rheumatic drugs,
including at least one tumour necrosis factor inhibitor. Low serum IgG
levels prior to Rituximab infusion has been identified as a risk factor for
severe infections in patients with rheumatoid arthritis. Decreased
levels of IgG, IgM and IgA have also been associated with Rituximab
use over time. International consensus has advised that IgG levels are
monitored at baseline prior to intitial Rituximab treatment, and then
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Results: at the beginning of the study, all groups were similar by
radiologic changes (number of erosions and degree of joint space
narrowing (JSN)). After 2 yrs of treatment, number of erosions in MTX,
SS and CBT groups increased (p < 0.05), whereas in LF group there
was only a tendency in increasing of erosions quantity (p > 0.05).
Increased number of erosions in MTX and SS groups was 2.1 and 3.22
times higher vs LF group (p < 0.05); 1.48 and 2.28 times higher vs CBT
(p > 0.05). Additionally, the number of pts without erosive progression
was: for MTX - 51.9%, LF - 68.0%, CBT - 68.9%, for SS - 40.7%
(p < 0. 05 vs LF and CBT). Frequency of radiologic remission (absence
of increase in erosions number and JSN) was higher in LF (40.0%) vs
MTX group (25.0%), SS (33.3%) or CBT (31.0%) (p > 0.05). Rapid RA
progression ( 4 erosions per year) was significantly frequently in MTX
group (9.61%) and SS (18.5%) vs LF (0%, p <0.05 - 0.01 vs MTX and
SS) and CBT (3.44%, p <0.05 vs SS)(see Table 1).
All therapeutic strategies have equal efficacy on radiologic
progression in pts with early and very early RA, whereas in pts with
late RA LF and CBT resulted in greater improvement in rate of X-ray
progression vs SS and MTX (p <0.05). LF, SS and CBT were equally
effective in pts with various disease duration, whereas pts with late
RA received MTX had more significant radiologic progression vs very
early RA.
Conclusions: Two yrs treatment with LF or CBT is more effective in
slowing joints damage vs MTX or SS. Initiation time of DMARDs is
important for MTX (results are much better for pts with very early RA),
while LF and CBT are equally effective for any disease duration.
iii123
iii124
Wednesday 2 May 2012, 10.45 – 11.45
196. METHOTREXATE MONITORING: INITIAL EXPERIENCE
WITH TRANSIENT ELASTOGRAPHY (FIBROSCAN)
Mark Lloyd1, Ayesha Ahmed2, Samantha Readhead2 and Aftab Ala2
Rheumatology, Frimley Park Hospital, Frimley, United Kingdom;
2
Hepatology, Frimley Park Hospital, Frimley, United Kingdom
1
Background: Methotrexate (MTX) is known to be hepatotoxic but
the risk of fibrosis is believed to be low. However, we and others have
published cases who have developed fibrosis with minimal or no
change on liver function tests(LFTs) or ultrasound (US). Because of this
experience we have developed a low threshold for investigating MTX
treated patients in more detail.
Methods: Transient elastography (FibroScan) is a relatively new but
well validated technique which measures liver elasticity by using
ultrasound to detect a low frequency shear wave. Increased stiffness
corresponds to fibrosis. The technique is quick (approximately 15 min
per patient), painless and training takes only hours. Levels > 7 kPa
suggest increased liver stiffness. Procollagenase 3 (P3NP) is a serum
marker of fibrogenesis. Levels > 5.5ug/L suggest high levels. Use in RA
has been limited by the confounding factors of bone erosions and
inflammation. However, low levels may offer some reassurance.
Results: We have scanned 15 patients. 11 female, 4 male. 14 RA, 1
PsA. Mean age 67yr. Mean duration of MTX 8 yr, mean total dose
5.3 g. 2 patients had diabetes, 1 had a history of alcohol consumption
>20 u/week (84 u/week). Scans were performed for a number of
clinical reasons (more than one in some patients): duration of MTX >10
yr (9 patients); P3NP >5.5 ug/L (12 patients); abnormal liver ultrasound
(3 patients) and previous alcohol excess (1 patient). 5 patients had a
fibroscan stiffness of >7 kPa (max 14.3). Mean total MTX dose in this
group was 3.1 g, vs 6.4 g in the < 7 kPa group. Of the >7 kPa group 1
patient had a history of alcohol excess; 2 were diabetic. 4 had
P3NP > 5.5ug/L but only 1 had abnormal LFTs (ALP 152) and only 1
out of 5 US scans was abnormal (fatty liver in a patient in whom biopsy
subsequently showed fibrosis).Because of the findings MTX was
stopped in 4 of the 5 patients.
Conclusions: This pilot work shows potential for the use of FibroScan,
possibly in conjunction with serum markers of liver fibrosis, in the
assessment of MTX liver toxicity. Where we had biopsy evidence of
fibrosis FibroScan supported this; liver US and routine LFTs appear to
have low sensitivity. Although this is a small study the lack of
association between MTX dose and liver stiffness suggests other risk
factors may be implicated in MTX fibrosis. The high (up to 30%) and
increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in
the general population, increasing polypharmacy and relaxation of
alcohol intake guidance for MTX treated RA patients suggest we
should consider more sensitive assessments of liver function in certain
MTX treated patients.
TABLE 1 Characteristics of patients with increased liver stiffness
Age
Total MTX
dose (g)
LFTs
US liver
P3NP
70
61
60
70
75
5.2
5.2
0.6
2.1
2.6
Normal
Normal
Normal
ALP 152
Normal
Normal
Normal
Normal
Normal
Fatty liver
5.2
5.9
6.4
7.4
9
FibroScan
stiffness (kPa)
8.7
8.9
14.3
7.3
12.1
Disclosure statement: All authors have declared no conflicts of
interest.
197. AN AUDIT OF HEPATITIS B SEROLOGY IN PATIENTS
RECEIVING TNF-a BLOCKADE AND THE UNCERTAIN ROLE
OF PROPHYLACTIC THERAPY IN THOSE WITH EVIDENCE OF
PAST INFECTION
Matthew Fittall1, Jessica Manson1 and Yiannis Ioannou1
1
Rheumatology, UCLH, London, United Kingdom
Background: Hepatitis B has the potential to lie dormant in previously
infected patients through the formation of covalently closed circular
DNA (cccDNA). It is believed that TNF-a mediates a protective role in
preventing reactivation but it is unknown what risks its blockade may
present to those with evidence of HBV past infection and proven
immunity. In such patients undergoing bone marrow transplantation,
reactivation of HBV may occur often with fatal consequences and thus
patients are treated prophylactically. However the role of prophylactic
therapy in patients receiving TNF-a blockade remains uncertain.
Methods: We carried out an audit of screening for viral hepatitis and
HIV in patients seen in the UCLH biologics clinic between Jan-Dec
2010. We also investigated the outcomes and management given to all
rheumatology patients who had abnormal hepatitis serology. Finally,
we undertook a literature search for published outcomes in patients
with evidence of hepatitis seropositivity in an effort to define best
practice.
Results: 81 patients were seen in the UCLH biologics clinic between
Jan and Dec 2010. All of these patients were screened for Hepatitis B
and C whilst 40/81 (49%) were screened for HIV. 8 (9.9%) had
serological evidence of vaccination to HBV, 3 (3.7%) had evidence of
past infection (HBsAg-ve, HBcAB þ ve), whilst no Hepatitis C nor HIV
infections were detected. A further 5 patients had tested positive for
past HBV infection between May 2009 and February 2011. Of these 8
patients with evidence of cleared infection, 5 had already been treated
with TNF-a blockade for a median of 36 months without prophylaxis
and without any apparent ill effect. All patients were subsequently
referred to hepatology and were given varying advice; predominantly
for lamivudine prophylaxis one month prior and throughout therapy. In
the literature there are 189 cases published in 7 separate series of
similar HBV sAg-ve/cAB þ ve patients who were not given prophylaxis
during a minimum of 12 months TNF-a blockade. There were 8 (4.2%)
reported cases of reactivation one of which proved fatal and in most
other cases HBsAB titres declined during TNF-a blockade.
Conclusions: Our audit of routine screening identified several patients
with evidence of past HBV infection who are at theoretical risk of
hepatitis B reactivation when given TNF-a blockade. Clear guidance as
to how to manage these patients is lacking, particularly as to whether
prophylaxis is warranted and if so in what form and for how long.
Though therapy without prophylaxis may be safe in most cases,
reactivation has been reported in the literature and the consequences
may be very severe and even fatal, thus underlining the need for
definitive guidance. UCLH is forming a local users group including
representatives from the relevant specialties to create local guidelines
on viral hepatitis and anti-TNF agents.
Disclosure statement: All authors have declared no conflicts of
interest.
198. ABATACEPT CONFERS CLINICAL EFFICACY
REGARDLESS OF BASELINE CRP STATUS IN PATIENTS WITH
RHEUMATOID ARTHRITIS AND INADEQUATE RESPONSE
TO METHOTREXATE IN THE AIM TRIAL
Jean Sibilia1, Rene´ Marc Flipo2, Bernard Combe3, Corine Gaillez4,
Manuela Le Bars4, Coralie Poncet5, Ayanbola Elegbe6 and
Rene Westhovens7
1
Department of Rheumatology, Louis Pasteur University, Strasbourg,
France; 2Department of Rheumatology, Centre Hospitalier
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
subsequently prior to each infusion. This study aims to assess compliance with current international consensus for the monitoring of
immunoglobulin levels in patients with RA receiving Rituximab therapy
in a university teaching hospital, and the frequency of adverse events
in relation to low immunoglobulin levels.
Methods: All patients with RA who had received Rituximab therapy
(2007 onwards) were identified. Dates of Rituximab infusions and
serum immunoglobulin measurements were obtained from electronic
systems. Adverse events and reasons for stopping Rituximab therapy
were obtained from clinical records. Reference ranges for serum
immunoglobulin levels were obtained from the hospital clinical
immunology department; normal range IgG 6.0-16.0 g/L; IgA 0.84.0 g/L; IgM 0.50-2.0 g/L.
Results: 105 patients with RA received at least 1 cycle of Rituximab
(number of cycles received: 1-6). Baseline immunoglobulin levels were
checked in 34/105 patients (32.4%). Immunoglobulin monitoring at
baseline and prior to each subsequent infusion was performed in 28/
105 (26.7%). Rituximab treatment was stopped in 35/105 (33.3%)
patients; no response n ¼ 21; allergic reaction n ¼ 7; low immunoglobulins n ¼ 4; gastrointestinal disturbance n ¼ 2; skin rash n ¼ 1.
Low serum IgG levels (<6.0 g/L) were identified in 5 patients
(IgG range 3.97 - 5.89 g/L), none of whom had documented serious
infections. 1 case developed recurrent sinusitis. Rituximab was
stopped in 4/5 of these patients; 1 patient was diagnosed with
MGUS and continued on treatment. Detection of low serum IgG levels
was identified in all patients following at least 2 Rituximab infusions
(n ¼ 2-5 cycles); 3 patients did not have baseline immunoglobulins
checked so the exact timing of low IgG levels is unclear.
Conclusions: Immunoglobulin monitoring in patients with RA on
Rituximab is an important method of preventing adverse events
including serious infection. Further research is needed into the
consequences of hypogammaglobulinaemia and what constitutes an
acceptable lower limit of immunoglobulins prior to further Rituximab
therapy. No serious infections were seen in the 5 severely hypogammaglobuminaemic patients in our trust receiving Rituxumab.
Disclosure statement: All authors have declared no conflicts of
interest.
POSTER VIEWING II
POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
iii125
TABLE 1.
CRP <1.2
CRP 1.2-<2.1
CRP 2.1-<4.0
CRP 4.0
Month 12
Abatacept
n ¼ 83
Placebo
n ¼ 46
Abatacept
n ¼ 88
Placebo
n ¼ 38
Abatacept
n ¼ 96
Placebo
n ¼ 40
Abatacept
n ¼ 104
Placebo
n ¼ 32
DAS28 remission
Est. of diff.
DAS28-LDAS
Est. of diff.
SDAI
Est. of diff.
SDAI-LDAS
Est. of diff.
37
33
57
44
21
18
57
35
4 (1, 15)
21 (12, 29)
21 (5, 36)
33 (23, 43)
17 (-2, 36)
9 (3, 15)
9 (-2, 20)
42 (32, 52)
29 (9, 49)
0 (0, 0)
26 (17, 35)
24 (7, 40)
47 (37, 57)
39 (20, 59)
8 (3, 14)
6 (-5, 17)
48 (38, 58)
38 (18, 58)
3 (0, 13)
20 (13, 28)
17 (0, 34)
39 (29, 48)
26 (5, 47)
5a (0.7, 9)
2 (-9, 12)
45* (35, 54)
23 (1, 44)
3 (0, 16)
(27,48)
(16, 50)
(46, 67)
(24, 63)
(12, 29)
(4, 33)
(46, 67)
(15, 55)
13 (3, 23)
2 (0.1, 12)
22 (10, 34)
16 (4, 27)
0 (0, 0)
13 (2, 24)
8 (2, 20)
3 (0.1, 13)
10 (3, 24)
13 (4, 29)
3 (0, 16)
22 (8, 36)
a
Data are % (95% CI) n ¼ number of patients with available data at Month 12; n ¼ 103.
Background: In RA, levels of acute phase reactants are correlated
with disease activity and joint destruction. It was previously shown that
tocilizumab confers improved response in patients with higher baseline C-reactive protein (CRP) level. In the AIM trial, overall high
proportions of patients achieved remission and Low Disease Activity
State (LDAS) when treated with abatacept; however, the effect of
baseline CRP has not been established. Here, we investigate whether
baseline CRP level affects clinical efficacy of abatacept treatment over
12 months.
Methods: Patients in the double-blind AIM trial (NCT00048568) were
randomized and treated with abatacept or placebo, plus background
MTX. Patients had active RA and inadequate response to MTX. The
proportions of patients achieving remission and LDAS defined by
Disease Activity Score 28 (DAS28), Simplified Disease Activity Index
(SDAI) and Clinical Disease Activity Index (CDAI) (<2.6 and 3.2, 3.3
and 11, 2.8 and 10, respectively) were evaluated according to
baseline CRP quartile: <1.2, 1.2-<2.1; 2.1-<4.0 and 4.0 mg/dL.
These post-hoc analyses are based on as-observed data.
Results: The proportions of patients achieving efficacy outcomes, by
baseline CRP quartile, along with estimate of difference at Month 12
are shown (table); similar proportions of patients achieved CDAIdefined outcomes.
Higher proportions of abatacept patients achieved LDAS and
remission according to DAS28, SDAI and CDAI compared with
placebo across all four baseline CRP quartiles, although outcomes
appeared numerically better in the lowest quartile for SDAI and DAS28,
confirming the important weighting of CRP in the calculation of these
outcomes. Treatment effects versus placebo were generally significant
across all CRP quartiles (95% CIs did not cross zero), except for the
most stringent outcomes.
Conclusions: Abatacept provides consistent efficacy across DAS28,
SDAI and CDAI outcomes, regardless of baseline CRP level.
Disclosure statement: B.C. received consultancy fees from Pfizer,
Schering, Roche and UCB, research grants from Pfizer, Schering and
UCB, and is a member of the speakers bureaus of Pfizer, Schering and
Roche. A.E. is an employee of, and has stock, stock options or bond
holdings in, Bristol-Myers Squibb. C.G. is an employee of, and has
stock, stock options or bond holdings in, Bristol-Myers Squibb. M.L. is
an employee of, and shareholder in, Bristol-Myers Squibb. R.W.
received consultancy fees from Bristol-Myers Squibb, Centocor,
Roche and Schering-Plough, research grants from Roche and UCB,
and is a member of the speakers bureau of Bristol-Myers Squibb. All
other authors have declared no conflicts of interest.
199. WHAT IS THE ROLE OF SUBCUTANEOUS
METHOTREXATE IN THE TREATMENT OF RHEUMATOID
ARTHRITIS?
Roya Hassanzadeh1, Clodagh Mangan1, Janice France2 and
Sandeep Bawa2
1
School of Medicine, Glasgow University, Glasgow, United Kingdom;
2
Dept of Rheumatology, Gartnavel General Hospital, Glasgow,
United Kingdom
Background: Methotrexate (MTX) is widely employed as the mainstay
drug in the treatment of rheumatoid arthritis (RA) and is currently
available for either oral or parenteral administration. In recent years,
biologic therapies such as tumour necrosis factor alpha inhibitors (antiTNFa) have become increasingly popular.
Although, current guidelines encourage the use of MTX as first line
therapy, the route of administration is not specified. Previous studies
have suggested that patients may be successfully treated with
subcutaneous (S/C) MTX where they have been unsuccessful on the
oral preparation, preventing the need for expensive biologic therapy.
Treatment with anti-TNFa is also associated with more severe side
effects, including reactivation of TB and the occurrence of opportunistic infections.
Methods: We carried out a retrospective analysis of 301 RA patients at
Gartnavel General Hospital, Glasgow, to explore the possible financial
and health benefits of using S/C MTX before resorting to anti-TNF
therapy. The patients had an average age of 57 (age range 17 - 84) and
a female male ratio of 3:1. We identified the patients who had been on
anti-TNFa and those who had been on S/C MTX using case records
from the respective clinics.
Results: A total of 68 patients (23%) and 256 patients (85%) of the
total cohort had tried S/C MTX and anti-TNFa therapy respectively.
Most patients had switched to S/C from oral MTX because it was
ineffective or intolerable due to adverse effects. Of the 68 patients who
had tried S/C MTX, 29% had subsequently discontinued treatment,
mostly due to continued adverse effects. Of the remaining patients still
on S/C MTX, 22% were also on anti-TNF therapy, while 49% were
established and stable on S/C MTX alone. Therefore, we can take 49%
as the success rate of S/C MTX in our cohort.
Of the 256 RA patients on anti-TNF therapy, 91% (233) had never
been on S/C MTX. Using the previously calculated success rate of
49%, we can estimate that the disease activity of 114 patients could
have been successfully controlled with S/C MTX, preventing the need
for biologic therapy. Based on the difference in cost between the two
treatment regimes, this can be translated into a potential cost saving
for our cohort of £950,000 per year.
Conclusions: Expenditure on biologic therapy is increasing exponentially, which is of concern in our current financial climate. If as we
suspect the underuse of S/C MTX is a national trend, the potential cost
savings to the NHS could stretch into hundreds of millions of pounds if
our observations were reproduced. We propose that national guidelines should stipulate that S/C MTX be tried if there is intolerability or
inefficacy with the oral preparation. If this were tried before resorting to
biologic therapy it would not only increase financial savings dramatically but also reduce patient exposure to a potentially harmful drug.
Disclosure statement: All authors have declared no conflicts of
interest.
200. CERTOLIZUMAB PEGOL IN PATIENTS WITH ACTIVE
RHEUMATOID ARTHRITIS ALIGNED WITH NICE GUIDANCE
FOR ANTI-TNF THERAPY: POST-HOC ANALYSES OF THE
REALISTIC PHASE IIIB RANDOMIZED CONTROLLED STUDY
M. E. Weinblatt1, R. Fleischmann2, R. van Vollenhoven3, P. Emery4,
T. W. J. Huizinga5, R. Goldermann6, B. Duncan7, J. Timoshanko8,
K. Luijtens9, O. Davies9 and M. Dougados10
1
Brigham and Women’s Hospital, Boston, Massachusetts, United
States of America; 2Metroplex Clinical Research Center, University of
Texas/Southwestern Medical Center, Dallas, Texas, United States of
America; 3Karolinska Institute, Stockholm, Sweden; 4University of
Leeds, Leeds, United Kingdom; 5Leiden University Medical Centre,
Leiden, Netherlands; 6UCB Pharma, Monheim, Germany; 7UCB
Pharma, Raleigh, North Carolina, United States of America; 8UCB
Pharma, Slough, United Kingdom; 9UCB Pharma, Brussels, Belgium;
10
Rene´ Descartes University, Paris, France
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Universitaire de France, Lille, France; 3Immuno-Rheumatology,
Hoˆpital Lapeyronie, Montpellier, France; 4Medical Affairs, BristolMyers Squibb, Rueil-Malmaison, France; 5Department of
Biostatistics, Docs International, Se`vres, France; 6Global Biometric
Sciences, Bristol-Myers Squibb, Princeton, New Jersey, United
States of America; 7Department of Rheumatology, UZ Gasthuisberg,
Leuven, Belgium
iii126
Wednesday 2 May 2012, 10.45 – 11.45
POSTER VIEWING II
TABLE 1.
Group (n: CZP, PBO)
ACR20 response
vs PBO (%)
LS mean change
from BL in DAS28(CRP)
LS mean change
from BL in DAS28(ESR)
LS mean change in
BL in HAQ-DI
Overall (851, 212)
BL-HDA (770, 197)
BL-HDA þ 2 prior
DMARDs (369, 86)
BL-HDA þ 2 prior
DMARDs þ anti-TNF
naive (134, 29)
51.1*a vs 25.9
50.8c vs 26.9
49.9c vs 24.4
1.64*b vs 0.79
1.68c vs 0.82
1.69c vs 0.91
1.82c vs 0.88
1.86c vs 0.93
1.80c vs 0.95
0.43*b vs 0.21
0.44c vs 0.23
0.44c vs 0.26
54.5c vs 20.7
1.88c vs 0.80
1.94c vs 0.80
0.48c vs 0.10
LS, least square; HDA, high disease activity (DAS28>5.1). *p < 0.001; aprimary analysis; bsecondary analysis; cpost-hoc analysis (p value not reported); ACR responses
determined with NRI; HAQ-DI and DAS28 used LOCF.
201. RHEUMATOID ARTHRITIS AND PHYSIOTHERAPY:
A NATIONAL SURVEY CONDUCTED BY THE NATIONAL
RHEUMATOID ARTHRITIS SOCIETY AND THE CHARTERED
SOCIETY OF PHYSIOTHERAPY
Jamie Hewitt1
1
National Rheumatoid Arthritis Society, Maidenhead,
United Kingdom
Background: Physiotherapy can help to alleviate some symptoms of
rheumatoid arthritis (RA), and equip those who have the disease with
useful knowledge to protect and strengthen their joints as much as
possible. As a result, clinical guidelines across the UK recommend that
every RA patient is given access to a physiotherapist, operating as part
of a multidisciplinary team, with a regular review. NRAS conducted a
member survey to examine the extent to which these clinical
guidelines are being adhered to.
Methods: The research involved conducting a literature review about
the medical evidence and public policy framework governing the use
of physiotherapy in the treatment of RA. NRAS then sent out 2,303
electronic questionnaires to NRAS members with RA in August 2011.
Survey questions focused on benefits of the treatment, how long they
waited for referral, how they were referred and how the service was
configured locally. A hard copy version of the questionnaire was also
sent to a randomly selected NRAS community-based group during
September 2011. In total 248 questionnaires were returned. 3
questionnaires and incomplete responses were cleansed from the
data. The total response rate of useable questionnaires was 10.6% out
of 2,303. Assuming respondents were representative of the sample
population then, with 95% confidence intervals, this gave an error
range of 6% when calculating proportions. This survey was therefore
intended to yield suggestive rather than conclusive evidence.
Results: The main age categories for respondents were 56-65 year
olds (39.6%), 46-55 year olds (24.1%) and 36-45 year olds (14.3%),
similar to the distribution in the general RA population. 86.1% were
female and 13.9% were male, slightly higher than the ratio observed in
the general RA population. 32.2% waited over a year for a
physiotherapy referral after being diagnosed with RA, while 31% had
never been referred. 21.9% said they could self-refer, significantly
lower than the figure identified in the literature review. 51.5% thought
their physiotherapist was working as part of a consultant-led multidisciplinary team and 13% were unsure. 47.9% regarded the service
as being part of the ongoing management of their disease. 65.7% felt
physiotherapy either moderately or strongly improved the function of
the parts of their body affected by RA and 58.6% felt physiotherapy
either moderately or strongly improved their mobility. Overall, 70.4%
rated the quality of the physiotherapy they received as good or very
good.
Conclusions: The survey suggests that a significant proportion of
medical practitioners are not complying with the best practice
stipulated in clinical guidelines by failing to give all RA patients
access to a physiotherapist, working as part of a multidisciplinary
team, with a regular review.
Disclosure statement: All authors have declared no conflicts of
interest.
202. BED-TIME SINGLE DOSE PREDNISOLONE IN
CLINICALLY STABLE RHEUMATOID ARTHRITIS PATIENTS
Mohammadbagher Owlia1
Medicine, Shahid Sadoughi University of Medical Sciences, Yazd,
Islamic Republic of Iran
1
Background: Sign and symptoms of rheumatoid arthritis have
circadian rhythms and are more prominent in the early morning in
most patients. Therefore, the timing of glucocorticoid administration
may be important with respect to the natural secretion of endogenous
glucocorticoids. In this study, we intended to test the hypothesis that
bedtime administration of oral prednisolone could be more efficient in
controlling signs and symptoms in patients with RA
Methods: Sixty rheumatoid arthritis patients with stable disease were
treated with low dose prednisolone at 8 a.m. for the first three months
and thereafter with similar dose at 10 p.m. for the next three months
(before-after method). We compared fatigue scores, morning stiffness
and pain scores, Clinical Disease Activity Indices (CDAI), erythrocyte
sedimentation rates (ESR), C Reactive Protein (CRP) level, and profile
of adverse effects
Results: Nine male (15%) and fifty-one female (85%), with a mean age
of 46 11.09 years, were included in the study. The mean of morning
stiffness, fatigue scores and CRP levels decreased when the
prednisolone was administrated at 10 p.m., and differences were
significant. Also the mean of CDAI was reduced at the end of the
second three months, when the patients were treated with prednisolone at night (P-value ¼ 0.000). The means of pain scores (Pvalue ¼ 0.146) and ESR (P-value ¼ 0.283) were decreased when the
patients took prednisolone at night, but there was no significant
statistical difference respectively.
Conclusions: Administration of low-dose oral prednisolone could
reduce disease activity scores in morning in clinically stable patients
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: In the REALISTIC (RA EvALuation In Subjects receiving
TNF Inhibitor Certolizumab pegol [CZP]) Phase IIIb trial, CZP was
associated with a rapid, consistent clinical response, with no new
safety signals, in a broad RA patient (pt) population. The National
Institute for Health and Clinical Excellence (NICE) in the UK
recommends anti-TNFs for adults who have failed treatment with
2 DMARDs, including methotrexate (unless contraindicated) and who
continue to have high disease activity ([HDA] DAS28>5.1). Here we
investigate the efficacy of CZP in pts who meet NICE criteria, using
data from the first 12 weeks (Wks) of the REALISTIC study.
Methods: In the REALISTIC trial (NCT00717236), active RA pts with
inadequate response to 1 DMARD were randomized to CZP (400 mg
Wks 0, 2, 4 then 200 mg every 2 wks), or placebo injections (PBO)
with current therapy. Pts were stratified by prior anti-TNF use,
concomitant methotrexate, and disease duration at randomization.
At study baseline, 38% of pts had previously been treated with an antiTNF. Here, pts were analysed based on baseline (BL) disease activity
(DAS28[ESR])-HDA, previous (2) DMARD exposure and previous
anti-TNF exposure (naive). This group represents those most likely
to be treated with an anti-TNF in the UK, as per the current NICE
guidance.
Results: Wk 12 ACR20 response rates were similar for CZP subgroups
(pts with BL-HDA [770], þ 2 prior DMARDs [396], þ anti-TNF naive
[134]) and the overall CZP group [851]. Improvements in Wk 12
responses in other clinical outcomes were also observed (compared
with PBO) (see table). Significant improvements in disease activity
and physical function occurred as early as Wk 2 in CZP treated pts. AE
and serious AE rates were comparable for CZP versus PBO.
Conclusions: CZP was associated with a rapid and consistent
clinical response in different subgroups of pts, those with BL-HDA
(DAS28>5.1), those with 2 prior DMARDs, and those that were antiTNF naive, who closely resemble pts in the UK who are eligible for antiTNF therapy as per the NICE guidance.
Disclosure statement: K.L. is an employee of UCB. O.D. is an
employee of, and holds stock options in, UCB. M.D. received research
grants from UCB, Abbott, Bristol-Myers Squibb, Pfizer and Roche, and
consultancy fees from UCB, Abbott, Bristol-Myers Squibb, Pfizer and
Roche. B.D. is an employee of, and holds stock options in, UCB. P.E.
received grants/research support and consultancy fees from UCB.
R.F. received grants/research support and consultancy fees from
UCB. R.G. is an employee of UCB. T.J. received consultancy fees from
UCB. J.T. is an employee of UCB. R.V. received grants and
consultancy fees from UCB. M.W. received research grants from
UCB and Abbott, and consultancy fees from UCB, Abbott, Amgen,
Pfizer and Centocor. All authors have declared no conflicts of interest.
POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
iii127
TABLE 1.
RFþ
DAS28 remission
DAS28-LDAS
SDAI remission
SDAI-LDAS
HAQ response
ACR20
ACR50
RF
Abatacept þ MTX
Infliximab þ MTX
Abatacept þ MTX
Infliximab þ MTX
27.9
52.5
13.1
57.4
70.7
87.8
54.0
22.5
32.5
13.3
38.3
67.8
69.2
44.2
42.9 (16.9, 68.8) n ¼ 14
50.0 (23.8, 76.2) n ¼ 14
7.1 (0.2, 33.9) n ¼ 14
42.9 (16.9, 68.8) n ¼ 14
57.1 (31.2, 83.1) n ¼ 14
92.9 (66.1, 99.8) n ¼ 14
50.0 (23.8, 76.2) n ¼ 14
11.1
38.9
0 (0,
44.4
57.9
68.4
36.8
(19.9, 35.8) n ¼ 122
(43.6, 61.3) n ¼ 122
(7.1, 19.1) n ¼ 122
(48.6, 66.2) n ¼ 122
(62.7, 78.8) n ¼ 123
(82.0, 93.6) n ¼ 123
(45.3, 62.8) n ¼ 124
(15.0, 30.0) n ¼ 120
(24.1, 40.9) n ¼ 120
(7.3, 19.4) n ¼ 120
(29.6, 47.0) n ¼ 120
(59.4, 76.1) n ¼ 121
(60.9, 77.4) n ¼ 120
(35.3, 53.1) n ¼ 120
(1.4, 34.7) n ¼ 18
(16.4, 61.4) n ¼ 18
0) n ¼ 18
(21.5, 67.4) n ¼ 18
(35.7, 80.1) n ¼ 19
(47.5, 89.3) n ¼ 19
(15.2, 58.5) n ¼ 19
Data are % (95% CI).
with RA. So it could be supposed that administrating prednisolone at
the bedtime may permit the smallest possible dose.
Disclosure statement: All authors have declared no conflicts of
interest.
Maxime Dougados1, Corine Gaillez2, Manuela Le Bars2,
Coralie Poncet3, Ayanbola Elegbe4 and Michael Schiff5
1
Department of Rheumatology, Hoˆpital Cochin, Descartes
University, Paris, France; 2Medical Affairs, Bristol-Myers Squibb,
Rueil-Malmaison, France; 3Department of Biostatistics, Docs
International, Se`vres, France; 4Global Biometric Sciences,
Bristol-Myers Squibb, Princeton, New Jersey, United States of
America; 5Department of Rheumatology, University of Colorado,
Denver, Colorado, United States of America
Background: RA is a heterogeneous disease with a range of
phenotypes that have implications for treatment. Rheumatoid factor
(RF) can be a biomarker of disease severity and an indicator of
treatment response: rituximab has increased efficacy in RF-positive
(RFþ) versus -negative (RF-) patients (pts); the opposite is true for
infliximab. Using data from the previously reported ATTEST trial, we
investigate clinical efficacy with abatacept or infliximab in RFþ versus
RF- pts.
Methods: We assessed efficacy outcomes according to baseline
RF status for pts treated with either abatacept or infliximab, plus
background MTX, over 12 months in the double-blind, randomized,
controlled ATTEST study (NCT00095147). Pts with missing RF
values were not included. Efficacy outcomes include Disease Activity
Score 28 (DAS28), Simplified Disease Activity Index (SDAI), Health
Assessment Questionnaire (HAQ) and ACR response. Data are asobserved and analyses are post hoc.
Results: At baseline, 87.2% (136/156) and 84.8% (140/165) abatacept- and infliximab-treated pts, respectively, were RFþ, compared
with 10.9% and 13.3% who were RF-. Proportions (95% CI) of pts
achieving outcomes at Month 12 are shown for abatacept and
infliximab, for RFþ and RF- pts respectively (Table 1). In RFþ pts,
estimates of difference (95% CI) between abatacept and infliximab did
not cross zero for DAS28-Low Disease Activity State (LDAS) (20.0 [6.7,
33.2]), SDAI-LDAS (19.0 [5.6, 32.5]) and ACR20 (18.6 [7.5, 29.8]).
Overall, clinical outcomes show that abatacept and infliximab were
effective in both RFþ and RF- pts at Month 12. In RFþ pts, estimates
of difference (95% CI) did not cross zero for abatacept versus
infliximab in the less stringent outcomes (LDAS and ACR20). Data
should be interpreted with caution given the small sample size leading
to wide CIs. Furthermore, the study was not powered to detect
differences in this subgroup analysis between abatacept and
infliximab.
Conclusions: These data suggest that, at Month 12, abatacept is
efficacious in both RFþ and RF- pts, and may be more efficacious than
infliximab in RFþ pts. Further analysis in a larger pt population is
warranted.
Disclosure statement: M.D. received consultancy fees, research
grants and honoraria from Bristol-Myers Squibb, and is a member of
the speakers bureau of Bristol-Myers Squibb. A.E. is an employee of,
and has stock, stock options or bond holdings in, Bristol-Myers
Squibb. C.G. is an employee of, and has stock, stock options or bond
holdings in, Bristol-Myers Squibb. M.L. is an employee of, and
shareholder in, Bristol-Myers Squibb. M.S. received consultancy fees
from Bristol-Myers Squibb. All other authors have declared no conflicts
of interest.
Rieke Alten1, Jeffrey L. Kaine2, Edward Keystone3, Peter T. Nash4,
Ingrid Delaet5, Keqin Qi6 and Mark C. Genovese7
1
Rheumatology Department, Schlossparkklinik, Berlin, Germany;
2
Rheumatology, Sarasota Arthritis Center, Sarasota, Florida,
United States of America; 3Rebecca MacDonald Centre for Arthritis
and Autoimmune Disease, Mount Sinai Hospital, Toronto, Ontario,
Canada; 4Rheumatology Research Unit, University of Queensland,
Brisbane, Queensland, Australia; 5Global Clinical Research
Immunology, Bristol-Myers Squibb, Princeton, New Jersey, United
States of America; 6Global Biometric Sciences, Bristol-Myers
Squibb, Princeton, New Jersey, United States of America;
7
Division of Immunology and Rheumatology, Stanford University
Medical Center, Palo Alto, California, United States of America
Background: Biological therapies for RA can increase the risk of some
safety events such as infections, autoimmune events and malignancies. Furthermore, with subcutaneous (SC) biologicals, some patients
(pts) may experience injection-site reactions (ISRs), such as burning
and stinging. Integrated analyses of clinical trial data are important to
monitor these events over the long term. Here, we investigate such
events using integrated clinical trial data of SC abatacept in a large
group of pts with RA refractory to traditional DMARDs
Methods: Data from the short- and long-term periods of five SC
abatacept RA clinical trials were pooled; one Phase IIa, two Phase IIIb
randomized controlled trials (ACQUIRE, ALLOW), and two Phase IIIb
open-label studies (ATTUNE, ACCOMPANY). Safety events were
assessed for pts who received 1 dose of SC abatacept (125 mg/
week fixed dose). Overall and 6-monthly (up to Month 24) incidence
rates (IRs) were calculated as number of pts with events per 100 ptyears (pt-yrs) of exposure, with 95% CIs. IRs post Month 24 are not
shown due to low pt numbers at time of data analysis.
Results: The analysis included 1879 pts with 3086 pt-yrs of exposure.
Mean (range) exposure was 20 (2-56) months; 1191 pts had >18
months of exposure. Serious infections occurred at an IR (95% CI) of
1.94 (1.50-2.50), in 59 (3.1%) pts; the most frequent (IR >0.10) were
pneumonia (0.36 [0.20-0.65]), urinary tract infection (0.16 [0.07-0.39])
and gastroenteritis (0.13 [0.05-0.35]). TB, pulmonary TB and peritoneal
TB were recorded in 1 pt each (0.03 [0.00-0.23] each). Malignancies
excluding non-melanoma skin cancer occurred at an IR of 0.68 (0.451.05) in 21 (1.1%) pts. The most frequent (IR >0.10) malignancies were
basal cell carcinoma (0.46 [0.27-0.77]), breast cancer and squamous
cell carcinoma of skin (0.16 [0.07-0.39] each). Autoimmune events
occurred with an IR of 1.28 (0.93-1.75) in 39 (2.1%) pts. The most
frequent (IR >0.10) autoimmune events were psoriasis (0.29 [0.150.56]) and Sjo¨gren’s syndrome (0.19 [0.09-0.43]). IRs of serious
infections, malignancies and autoimmune events did not increase
with increasing exposure. ISRs occurred with an IR of 2.22 (1.74-2.82)
in 66 (3.5%) pts; the most frequent were erythema, haematoma, pain
and pruritus (0.46 [0.27-0.77] each). Events were mostly (94%) mild in
intensity; 2 pts discontinued due to ISRs. ISRs mainly occurred during
the first 6 months.
Conclusions: These pooled safety data, from 1879 pts with up to 4.5
yrs of treatment and 3086 pt-yrs of exposure, demonstrate that longterm treatment with SC abatacept is well tolerated, and does not lead
to an increase in infections, malignancies or autoimmune events over
time.
Disclosure statement: R.A. received research grants from BristolMyers Squibb, Merck, Wyeth and Pfizer, consultancy fees from Merck,
Abbott, Horizon, Novartis, Roche and Nitec, is a member of the
speakers bureaus of Bristol-Myers Squibb, Merck, Abbott, Horizon,
Novartis and Roche, and holds a non-remunerative position of
influence at Bristol-Myers Squibb, Abbott, Novartis and Roche. I.D.
is an employee of, and holds stock, stock options or bond holdings
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
203. CLINICAL EFFICACY OF ABATACEPT AND INFLIXIMAB
IN COMBINATION WITH METHOTREXATE ACCORDING
TO BASELINE RHEUMATOID FACTOR STATUS IN THE
ATTEST TRIAL
204. SAFETY PROFILE OF SUBCUTANEOUS ABATACEPT
FOCUSING ON CLINICALLY RELEVANT EVENTS IN PATIENTS
WITH RHEUMATOID ARTHRITIS AND UP TO 4.5 YEARS
OF EXPOSURE
iii128
Wednesday 2 May 2012, 10.45 – 11.45
POSTER VIEWING II
There was more use of high dose MTX in the Rem group but no
increased use of combination DMARDs, steroids or high dose MTX in
the MDA group. This may reflect patient choice or treatment
intolerance but may reflect failure to optimize treatment once NICE
anti-TNF response criteria have been met. Recognized limitations of
the DAS may also influence management decisions.
Of interest, most patients stayed in their original DAS response
category over time.
Disclosure statement: All authors have declared no conflicts of
interest.
in, Bristol-Myers Squibb. M.G. received consultancy fees from BristolMyers Squibb. J.K. received research grants from Bristol-Myers
Squibb, and is on the speakers bureaus of Amgen, Bristol-Myers
Squibb, Novartis and UCB. E.K. received consultancy fees from
Abbott, Amgen, Bristol-Myers Squibb, Centocor, Crescendo,
Genentech, Hoffmann-La Roche, Pfizer, Roche, Schering-Plough
and UCB, research grants from Abbott, Amgen, Bristol-Myers
Squibb, Centocor, Crescendo, Hoffmann-La Roche, Roche,
Schering-Plough, UCB, AstraZeneca, Novartis and Wyeth, is a
member of the speakers bureaus of Abbott, Amgen, Bristol-Myers
Squibb, Hoffmann-La Roche, Pfizer and Schering-Plough, and is an
investigator for Centocor. P.N. received consultancy fees, research
grants and honoraria from Bristol-Myers Squibb, and is a member of
the speakers bureau of Bristol-Myers Squibb. K.Q. is an employee of
Bristol-Myers Squibb.
206. SUBCUTANEOUS ABATACEPT VERSUS INTRAVENOUS
ABATACEPT IN PATIENTS WITH RHEUMATOID ARTHRITIS:
LONG-TERM DATA FROM THE ACQUIRE TRIAL
205. DISEASE ACTIVITY SCORE (DAS) RESPONSE TO
ANTI-TNF IN RA PATIENTS
Judith Clark1, Sally Kardash1, Ernest Wong1, Richard Hull1,
Fiona McCrae1, Ragai Shaban1, Lynn Thomas1, Steven Young-Min1
and Joanna Ledingham1
1
Rheumatology Department, Queen Alexandra Hospital, Portsmouth,
United Kingdom
Background: There is an increasing drive to use treat-to-target &
remission criteria in RA management. An analysis of DAS response
amongst anti-TNF treated RA patients in our District General Hospital
was undertaken
Methods: 200 anti-TNF treated RA patients were randomly selected.
Data was collected on patient demographics, pre anti-TNF disease
duration & treatment prescribed (anti-TNF drug(s), DMARDs &
steroids). DAS at initiation & after 6 months of anti-TNF, the 10 most
recent DAS & components of the most recent DAS were noted. Record
was made of how many patients met NICE response criteria for
ongoing anti-TNF therapy & had EULAR moderate disease activity
(MDA, DAS > 3.2), low disease activity (LDA, DAS > 2.6,3.2) or
remission (Rem, DAS 2.6)
Results: The mean age of patients was 59 (range 23-91) years & the
mean pre anti-TNF disease duration was 11 (range 1-56) years. All
patients met NICE criteria for starting anti-TNF therapy with a mean
pre-treatment DAS of 6.72 (range 5.15-9.81). 41 (21%) patients were
treated with Etanercept, 101 (51%) with Adalimumab & 58 (29%) with
Infliximab. Further results are shown in Table 1.
Although patients did move between response groups over time
the majority remained in the same response group at latest DAS
assessment as at 6 months after starting anti-TNF.
44 of those in Rem or LDA after 6 months on anti-TNF thereafter
developed MDA: 12 (27%) were on Etanercept (29% of those on the
drug), 18 (41%) were on Adalimumab (18% of those on the drug) and
14 (32%) were on Infliximab (24% of those on the drug).
On most recent DAS:
Background: Efficacy and safety of IV ABA is well established in RA.
ACQUIRE showed comparable safety and efficacy in SC vs IV ABA
over 6 mths; here, we present 18-mth data from the long-term
extension (LTE).
Methods: ACQUIRE was a Phase IIIb, 6-mth, double-blind (DB) study
(NCT00559585) of pts with active RA (10 swollen and 12 tender
joint count [SJC and TJC], CRP 0.8 mg/dL) refractory to MTX. Pts
were randomized to SC ABA (125 mg/week) with IV ABA loading
(10 mg/kg) on Day 1 or IV ABA (10 mg/kg) on Days 1, 15, 29 and
every 4 wks for 6 mths; all pts received MTX. After 6 mths pts could
enter the open-label LTE to receive SC ABA 125 mg/week. Safety,
immunogenicity (by electrochemiluminescence) and efficacy (ACR 20,
50 and 70 and HAQ-DI responses [improvement from baseline (BL)
0.3]) were assessed for pts treated with 1 dose of ABA. Efficacy
data are as-observed; not all pts reached later timepoints at time of
analyses.
Results: Of 1372 pts entering the LTE, 1222 (89.1%) remained on
therapy at time of reporting. Overall mean BL RA duration was 8 yrs,
TJC and SJC were 30 and 20, and HAQ-DI was 1.7; characteristics
were similar between groups. Median (SD) ABA exposure was 22 (3.8)
mths. The incidence rate (IR, events/100 pt-yrs) of SAEs was
comparable with that seen with SC ABA in the DB period (9.00 [95%
CI: 7.69-10.55] and 9.02 [6.31-12.90], respectively) and did not
increase with increasing exposure. The IR of overall and serious
All patients met NICE criteria to continue anti-TNF.
42%, 20% & 38% had MDA, LDA & were in Rem respectively.
Significantly more Rem patients were on at least 15 mg of MTX per
week (64%, p < 0.0001) than LDA (33%) & MDA patients (37%); no
other major differences in treatment amongst response groups were
identified.
Within the MDA group 33% had tender joint count 5, 10% had
swollen joint count 5, 23% had VAS 50 & 13% had ESR 30.
Some patients scored highly on more than one DAS component &
average DAS was 4.15.
Conclusions: This data shows remission is achievable with anti-TNF
therapy but many patients, despite meeting NICE anti-TNF response
criteria have ongoing high DAS.
TABLE 1.
Current
response
by DAS
Number
(%)
Anti-TNF drug
Etanercept
MDA DAS >3.2
LDA DAS 3.2, >2.6
Rem DAS 2.6
Total
84 (42)
40 (20)
76 (38)
200
20
11
10
41
(24)
(28)
(13)
(21)
Concurrent drugs
Adalimumab
32
21
48
101
(38)
(53)
(63)
(50)
Infliximab
32
8
18
58
(38)
(20)
(23)
(29)
MTX
^15 mg/wk
31
13
49
93
(37)
(33)
(65)
(47)
DAS at 6 months after
starting anti-TNF
MTX
<15 mg/wk
18
7
19
44
(21)
(18)
(25)
(22)
Other single
DMARD
14
6
9
29
(17)
(15)
(12)
(15)
Combination
DMARD
14
7
14
35
(17)
(18)
(18)
(18)
Steroid
Nil
14
5
10
29
5 (6)
5(13)
5 (7)
15 (8)
(17)
(13)
(13)
(15)
MDA
DAS >3.2
LDA DAS
3.2, >2.6
Rem DAS
2.6
40 (48)
9 (23)
8 (11)
57
28 (33)
22 (55)
19 (25)
69
16 (19)
9 (23)
49 (65)
74
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Mark C. Genovese1, Arturo Covarrubias Cobos2, Gustavo Leon3,
Eduardo F. Mysler4, Mauro W. Keiserman5, Robert M. Valente6,
Peter T. Nash7, J. Abraham Simon Campos8, Wieslawa Porawska9,
Jane H. Box10, Clarence W. Legerton III11, Evgeny L. Nasonov12,
Patrick Durez13, Ramesh Pappu14, Ingrid Delaet14, Julie Teng14 and
Rieke Alten15
1
Division of Immunology and Rheumatology, Stanford University
Medical Center, Palo Alto, California, United States of America;
2
Rheumatology, Medical Center of the Americas, Me´rida, Mexico;
3
Rheumatology, Instituto De Ginecologia Y Reproduccion, Lima,
Peru; 4Department of Rheumatology, Organizacion Medica de
Investigacio´n, Buenos Aires, Argentina; 5Internal Medicine
Department - Rheumatology Section, Pontiphycial Catholic
University, Porto Alegre, Brazil; 6Rheumatology, Arthritis Center of
Nebraska, Lincoln, Nebraska, United States of America;
7
Rheumatology Research Unit, University of Queensland, Brisbane,
Queensland, Australia; 8Rheumatology, Centro De Especialidades
Me´dicas, Me´rida, Mexico; 9Novamed, Poznan˜ski Ooerodek
Medyczny, Poznan, Poland; 10Arthritis & Rheumatology of the
Carolinas, Charlotte, North Carolina, United States of America;
11
Low Country Rheumatology, Charleston, South Carolina, United
States of America; 12Institute of Rheumatology, Russian Academy of
Medical Sciences, Moscow, Russian Federation; 13Department of
Rheumatology Saint-Luc, Universite´ Catholique de Louvain,
Brussels, Belgium; 14Global Clinical Research Immunology,
Bristol-Myers Squibb, Princeton, New Jersey, United States of
America; 15Rheumatology Department, Schlossparkklinik, Berlin,
Germany
POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
iii129
geographic region and according to time period (1995–1999, 2000–
2005, and 2006 to April 2010).
Results: Across all regions and within each time period, the proportion
of pts prescribed DMARDs or methotrexate increased between 3
months and 12 months. In contrast, the increase in combination
DMARDs prescription was less marked with either no or little increase
between 3-6 and 6-12 months but a modest overall increase between
3 and 12 months. DMARDs prescription at 12 months was analysed to
provide a snapshot of RA therapy: there was substantial regional
variation regardless of time period, ranging from: 19.29-49.06%
between 1995-1999; from 36.09-60.17% between 2000-2005; and
from 45.32-73.6% between 2006-April 2010. The regional differences
in the proportion of pts prescribed DMARD at 12 months ranged from
24-30% within each time period. Scotland and Northern Ireland had
the highest prescribing of DMARDs at 12 months (73.6% and 70.14%,
respectively). Prescribing patterns of all medications at 3 and 6 months
also varied from region to region regardless of time period. At 3
months, DMARD prescribing for regions in England from the most
recent time period (2006-April 2010) ranged from 27.49-53.62%, and
methotrexate from 15.6-40.65%. Corresponding data for Scotland and
Northern Ireland was 63.98% and 58.33% for DMARD prescribing,
and 23.29% and 47.92% for methotrexate. As part of the poster we
will present an interactive map of 3, 6 and 12 month data analysing
DMARD, methotrexate and combination DMARDs prescribing for all
13 regions across the UK.
Conclusions: Our data confirm the significant regional variation both
in the timing of DMARD or methotrexate therapy and in the proportion
of RA pts receiving these therapies at specific time points. Despite
NICE guidelines recommending combination DMARD treatment
(including methotrexate) as first-line therapy within 3 months of
persistent symptoms onset, at best, 2 in 5 RA pts in England appear
to be prescribed methotrexate at this time point. Identifying regions
demonstrating good practice and implementing successful prescribing
behaviour will help minimize regional variation, drive equity and
optimize the number of RA patients who achieve clinical remission.
Disclosure statement: N.A. received research funding from, and is a
member of the speakers bureaus of, Roche, Merck and Abbott. J.C.
received funding from MHRA, Wellcome Trust, Medical Research
Council, NIHR Health Technology Assessment Programme, Innovative
Medicine Initiative, UK Department of Health, Technology Strategy
Board, Seventh Framework Programme EU, and various universities,
contract research organizations and pharmaceutical companies. C.E.
received research funding from, and is a member of the speakers
bureaus of Roche, UCB, Abbott, GSK and Pfizer. C.H. is a project lead
for Roche, NHS Life Sciences Innovation Delivery Unit and NHS
National Programmes. I.S. is a freelance medical writer employed by
Roche. T.V. received funding from MHRA, Wellcome Trust, Medical
Research Council, NIHR Health Technology Assessment programme,
Innovative Medicine Initiative, UK Department of Health, Technology
Strategy Board, Seventh Framework Programme EU, and various
universities, contract research organizations and pharmaceutical
companies. All other authors have declared no conflicts of interest.
207. REGIONAL DIFFERENCES IN THE TREATMENT OF
RHEUMATOID ARTHRITIS IN THE UNITED KINGDOM
208. TEMPORAL TRENDS IN THE TREATMENT OF
RHEUMATOID ARTHRITIS (RA) IN THE UK WITH
REFERENCE TO BEST PRACTICE
Christopher J. Edwards1, Nigel Arden2,3, Jennifer Campbell4,
Tjeerd van Staa4, Claire Housden5 and Ify Sargeant6
1
Department of Rheumatology, University Hospital Southampton
NHS Foundation Trust, Southampton, United Kingdom; 2Nuffield
Department of Orthopaedics, Rheumatology and Musculoskeletal
Sciences, University of Oxford, Oxford, United Kingdom; 3University
of Southampton, University Hospital Southampton NHS Foundation
Trust, Southampton, United Kingdom; 4The General Practice
Research Database, Medicines and Healthcare Products Regulatory
Agency, London, United Kingdom; 5NHS Life Sciences Innovation
Delivery Unit and NHS National Programmes, Roche Products Ltd,
Welwyn Garden City, United Kingdom; 6Communications, ismedica
Ltd, Wrinehill, United Kingdom
Christopher J. Edwards1, Nigel Arden2,3, Jennifer Campbell4,
Tjeerd van Staa4, Claire Housden5 and Ify Sargeant6
1
Department of Rheumatology, University Hospital Southampton
NHS Foundation Trust, Southampton, United Kingdom; 2Nuffield
Department of Orthopaedics, Rheumatology and Musculoskeletal
Sciences, University of Oxford, Oxford, United Kingdom; 3University
of Southampton, University Hospital Southampton NHS Foundation
Trust, Southampton, United Kingdom; 4The General Practice
Research Database, Medicines and Healthcare Products Regulatory
Agency, London, United Kingdom; 5NHS Life Sciences Innovation
Delivery Unit and NHS National Programmes, Roche Products Ltd,
Welwyn Garden City, United Kingdom; 6Communications, ismedica
Ltd, Wrinehill, United Kingdom
Background: Disease-modifying anti-rheumatic drugs (DMARDs) are
effective in RA. Much data on DMARDs use is from the tertiary care
setting and it is unclear how well this reflects routine practice. This
study describes temporal and regional trends in drug therapy for RA
throughout the UK in the primary /secondary care setting.
Methods: Descriptive, cohort study with matched controls using the
UK General Practice Research Database (GPRD) of primary care
medical records. The analysis included 35,911 RA patients (pts) aged
18 years with a recorded diagnosis of RA between 01/01/1995 and
31/03/2010. Prescribing of DMARD, methotrexate or combination
DMARD within 3, 6 or 12 months was analysed according to
Background: Disease-modifying anti-rheumatic drugs (DMARDs)
have established efficacy in RA however data from over 34,000
primary care records indicates that only half of RA patients (pts)
between 1987-2002 received DMARD therapy (Edwards et al. 2005).
The current study was undertaken to provide an updated view of
DMARD prescribing in RA and to describe temporal trends in the UK
with reference to best practice.
Methods: Descriptive, cohort study with matched controls using the
UK General Practice Research Database (GPRD). The analysis
included 35,911 RA pts aged 18 years with a recorded diagnosis
of RA between 01/01/1995 and 31/03/2010. Medication prescribing
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
infections did not increase vs the DB period (47.64 [44.01-51.58] vs
84.62 [74.50-96.11] and 1.97 [1.41-2.74] vs 1.48 [0.62-3.56], respectively) and did not increase with increasing exposure. Opportunistic
infections in the LTE included 3 TB cases and 2 candidiasis cases; no
opportunistic infections were observed in the DB period. Injection-site
reactions occurred in 24 (1.7%) pts in the LTE (none serious). ABAinduced antibodies occurred in 39/1365 (2.9%) pts in the LTE; 4/11 pts
with anti-CTLA4 antibodies eligible for testing were positive for
neutralizing antibody. Immunogenicity did not affect efficacy, safety
or ABA pharmacokinetics. ACR responses to Mth 24 were maintained
from Mth 6 and comparable between original SC vs IV groups. DAS28
remission rates (95% CIs) were 24% (21-27) [n ¼ 685] vs 25% (22-28)
[n ¼ 688] at Day 169 and 32% (22-42) [n ¼ 85] vs 31% (20-41) [n ¼ 72]
at Day 729 in the original SC vs IV groups, respectively. HAQ
responses were 73% (69-76) [n ¼ 691] and 68% (65-72) [n ¼ 672] at
Day 169 and 63% (53-73) [n ¼ 87] and 56% (45-67) [n ¼ 77] at Day 729
in the original SC and IV groups, respectively. At analyses, most
patients had not completed the later timepoints (Days 617, 729).
Conclusions: Over 24 mths, SC ABA showed acceptable safety, with
high pt retention, similar to the IV experience. Efficacy was comparable
between SC and IV groups; ACR and HAQ responses and DAS28
remission rates were maintained in the LTE.
Disclosure statement: R.A. received research grants from BristolMyers Squibb, Merck, Wyeth and Pfizer, consultancy fees from Merck,
Abbott, Horizon, Novartis, Roche and Nitec, is a member of the
speakers bureaus of Bristol-Myers Squibb, Merck, Abbott, Horizon,
Novartis and Roche, and holds a non-remunerative position of
influence at Bristol-Myers Squibb, Abbott, Horizon and Roche. J.B.
received consultancy fees from Bristol-Myers Squibb, is a member of
the speakers bureau of Bristol-Myers Squibb, and is an owner of Box
Arthritis and Rheumatology of the Carolinas PLLC. A.C. is a principal
investigator for BMS, Lilly and Pfizer, and an owner of Unidad
Reumatologica Las Americas. I.D. is an employee of, and holds stock,
stock options or bond holdings in, Bristol-Myers Squibb. P.D. is a
member of the speakers bureau of Bristol-Myers Squibb. M.G. has
received consultancy fees from Bristol-Myers Squibb. M.K. has
received consultancy fees from Bristol-Myers Squibb, MSD and
Abbott, research grants from Bristol-Myers Squibb, MSD, Abott,
Biogen, Eli Lilly, Human Genome Sciences, Pfizer, Roche, UCB and
Novartis, and is a member of the advisory boards of Bristol-Myers
Squibb and MSD. C.L. received consultancy fees from Bristol-Myers
Squibb. E.M. received consultancy fees from Bristol-Myers Squibb, is
an investigator for Bristol-Myers Squibb, and is a member of the
speakers bureau of Bristol-Myers Squibb. P.N. received consultancy
fees, research grants and honoraria from Bristol-Myers Squibb, and is
a member of the speakers bureau of Bristol-Myers Squibb. E.N. is a
member of the speakers bureaus of Roche, Bristol-Myers Squibb,
Abbott, Merck and UCB. R.P. is an employee of Bristol-Myers Squibb.
J.T. is an employee of, and holds stock, stock options or bond
holdings in, Bristol-Myers Squibb. R.V. received research support from
Pfizer, UCB, BMS, Roche, Takeda and Eli Lilly. All other authors have
declared no conflicts of interest.
iii130
Wednesday 2 May 2012, 10.45 – 11.45
209. VARIATION IN THE USE OF BIOLOGICS IN THE
MANAGEMENT OF RHEUMATOID ARTHRITIS ACROSS
THE UNITED KINGDOM
Ernest Choy1, Sandra McAuliffe2, Kirsty Roberts3 and Ify Sargeant4
1
Section of Rheumatology, Department of Medicine, Cardiff
University School of Medicine, Cardiff, United Kingdom;
2
Consultancy, McAuliffe Interim Options Ltd, Oxfordshire,
United Kingdom; 3Market Insight and Analysis Group, Roche
Products Ltd, Welwyn Garden City, United Kingdom;
4
Communications, ismedica Ltd, Wrinehill, United Kingdom
Background: Unprecedented change has occurred in the management of moderate and severe rheumatoid arthritis (RA) over the last
decade, with the addition of more effective biologics to existing
disease-modifying antirheumatic drugs (DMARDs). Studies indicate
that there is variation in the use of and access to biologics and
adherence to treatment guidelines. There is limited data on variations
in the use of biologics at hospital and regional level in the UK and a
lack of literature with a longer follow-up period. This study aimed to
describe treatment patterns, adherence to guidelines and medical
outcomes at hospital and regional level in the UK.
Methods: This was a retrospective cohort study of RA patients (pts)
selected from 6 health regions and from 4 hospitals in each region,
including at least 1 major teaching hospital (TCH) and 2 or 3 district or
general hospitals (DGH). Treatment with DMARDs / biologics was
examined in comparison with NICE guidelines and in relation to
disease severity.
Results: A total of 588 pt records were analysed; 398 from 6 regions in
the DGH setting and 190 from 6 regions in the TCH. Regardless of
setting, there were substantial regional differences in the proportions
of pts receiving biologics (range 3-22%). NICE guidelines focus on
initiation of therapy and recommend combination DMARD/biologic
therapy; however 23-30% of pts were receiving biologic monotherapy.
Similar to biologic usage, across all regions and both settings, the
majority of pts (61%) were currently receiving one DMARD. Of 588
patients, 13% and 3% of patients were currently receiving two or three
DMARDs, respectively. There was a similar range and mix of DMARDs
used in both the DGH and TCH settings. NICE guidelines recommend
initiation of biologics in pts with active RA (DAS28 >5.1): average
DAS28 score on initiation of biologic therapy was above 6 in all
regions. The proportion of patients with an improvement in DAS28
post-biologic therapy was similar across all regions (range 88-100%).
DAS28 scores were well recorded at baseline and 6 months but not at
other time points.
Conclusions: Biologics usage varies across the UK: identifying the
reasons for these variations will help to standardize and optimize care
of pts with RA who achieve clinical remission, the ultimate goal of
treatment. Around one quarter of pts receive monotherapy with
biologic despite national guidelines recommending combination
DMARD/biologic treatment. This could reflect withdrawal of DMARD
due to intolerance or achievement of disease remission, or could
indicate non-compliance. Furthermore, routine monitoring of DAS28
requires optimization in order to inform timely escalation of treatment
and ensure efficient use of healthcare resources by ensuring pts
continue to respond to treatment.
Disclosure statement: E.C. received research grants and consultancy fees from, and is a member of the advisory boards and speakers
bureaus of, Abbott, Chugai, MSD, Pfizer, Roche, Schering Plough,
UCB and Wyeth. S.M. provided data analysis to Roche. K.R. is a
market analysis manager for Roche. I.S. is a freelance medical writer
employed by Roche.
210. RELATIVE EFFICACY OF RITUXIMAB VERSUS AN
ALTERNATIVE TNF INHIBITOR IN PATIENTS WITH
RHEUMATOID ARTHRITIS AND AN INADEQUATE RESPONSE
TO A SINGLE PREVIOUS TNF INHIBITOR: INTERIM RESULTS
FROM SWITCH-RA, A GLOBAL, COMPARATIVEEFFECTIVENESS, OBSERVATIONAL STUDY
Paul Emery1,2, Piercarlo Sarzi-Puttini3, Robert J. Moots4,
Alexandros Andrianakos5, Thomas P. Sheeran6, Denis Choquette7,
Axel Finckh8, Marie-Laetitia Desjuzeur9, Eric K. Gemmen10,
Chiedzo Mpofu9 and Jacques-Eric Gottenberg11
1
Division of Musculoskeletal Disease, Leeds Institute of Molecular
Medicine, University of Leeds, Leeds, United Kingdom; 2NIHR Leeds
Musculoskeletal Biomedical Research Unit, Leeds Teaching
Hospitals NHS Trust, Leeds, United Kingdom; 3Rheumatology Unit, L
Sacco University Hospital, Milano, Italy; 4Clinical Sciences Centre,
University of Liverpool, Liverpool, United Kingdom; 5Hellenic
Foundation for Rheumatological Research, Athens, Greece;
6
Rheumatology Department, Cannock Chase Hospital, Cannock,
United Kingdom; 7Rheumatology Department, University of
Montreal, Notre-Dame Hospital, Montreal, Quebec, Canada;
8
Department of Medical Specialties, Division of Rheumatology,
University Hospital of Geneva, Geneva, Switzerland; 9F Hoffmann-La
Roche Ltd, Basel, Switzerland; 10Quintiles Inc, Rockville, Maryland,
United States of America; 11Department of Rheumatology, CHU
Strasbourg, Strasbourg, France
Background: Data from a longitudinal cohort study suggested that,
following an inadequate response to a tumour necrosis factor inhibitor
(TNFi), switching to rituximab (RTX) as opposed to an alternative TNFi
may provide greater efficacy (Finckh A, et al. Ann Rheum Dis
2010;69:387-393). Here we present data from an interim analysis of
SWITCH-RA, an ongoing global, multicentre, prospective, observational study in patients with rheumatoid arthritis (RA) and an
inadequate response or intolerance to a single previous TNFi in
routine clinical practice.
Methods: The current analysis examined the relative efficacy of RTX
compared with an alternative TNFi in patients with data available at 6
months. The conditional probability of receiving RTX vs alternative
TNFi treatment was assessed using propensity scores. Following
commencement of new therapy, changes in DAS28-ESR and ESR at 6
months were compared in the treatment groups using analysis of
covariance, controlling for baseline value, propensity score and other
covariates found to significantly differ at baseline.
Results: As of Feb 2011, 660 patients in 9 countries had completed 6
months’ treatment. The 362 RTX and 298 alternative TNFi patients
were mostly female (79.2%) and had a mean age of 55.4 y. Mean (SD)
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
was analysed by time period and pre-post national NICE clinical
guidance publication.
Results: Between 1995 (baseline) and 2010, there has been a
substantial increase in DMARD and methotrexate prescribing across
the UK with a less marked increase in combination DMARD
prescribing. Taking 12-month prescribing as a snapshot: DMARD
prescribing was 19-49% at baseline increasing to 45-74% by 2006April 2010; methotrexate prescribing was 4-16% at baseline increasing
to 32-60%; combination DMARD prescribing was 0-8% at baseline
increasing to 3-17%. The increase at 12 months was also evident
at 3 and 6 months. Median time from diagnosis to treatment with
DMARD (n ¼ 5,513), methotrexate (n ¼ 3,754) or combination DMARD
(n ¼ 1,310) was 50, 119 and 560 days, respectively. NICE guidelines for
RA (CG79) were published in February 2009 and recommend
combination DMARD treatment (including methotrexate) as first-line
therapy within 3 months of the onset of persistent symptoms.
Prescribing behaviour two years prior to and one year after NICE
guideline publication was evaluated. Between March 2007-February
2008, March 2008-February 2009, and March 2009-February 2010, the
proportion of RA patients prescribed DMARDs was 43.79%, 47.23%
and 51.14%, respectively. The increase in DMARD prescribing was
gradual with no evidence of a rapid increase post-NICE guideline
publication. Comparing the year prior to and the year post NICE
guideline publication methotrexate prescribing increased from 27.72%
to 35.24% and combination DMARD prescribing from 3.55% to 6.52%
suggesting a potential small impact.
Conclusions: Between 1995 and 2010 there was a substantial
increase in DMARD and methotrexate prescribing and a less marked
increase in combination DMARD prescribing. Despite this increase, a
large number of patients with RA appear to be under-treated
according to clinical recommendations and guidelines. The publication
of NICE guidelines appears to have had little impact on prescribing.
There is a need to optimize roll-out and implementation of these highquality guidelines to ensure patients achieve the best possible disease
control; systems and processes for monitoring implementation should
be developed.
Disclosure statement: N.A. received research funding from, and is a
member of the speakers bureaus of, Roche, Merck, and Abbott. J.C.
received funding from MHRA, Wellcome Trust, Medical Research
Council, NIHR Health Technology Assessment programme, Innovative
Medicine Initiative, UK Department of Health, Technology Strategy
Board, Seventh Framework Programme EU, and various universities,
contract research organizations and pharmaceutical companies. C.E.
received research funding from, and is a member of the speakers
bureaus of, Roche, UCB, Abbott, GSK and Pfizer. C.H. is a project lead
for Roche, NHS Life Sciences Innovation Delivery Unit and NHS
National Programmes. I.S. is a freelance medical writer employed by
Roche. T.V. received funding from MHRA, Wellcome Trust, Medical
Research Council, NIHR Health Technology Assessment programme,
Innovative Medicine Initiative, UK Department of Health, Technology
Strategy Board, Seventh Framework Programme EU, and various
universities, contract research organizations and pharmaceutical.
All other authors have declared no conflicts of interest.
POSTER VIEWING II
POSTER VIEWING II
211. COMMISSIONER QUALITY METRICS IN RHEUMATOID
ARTHRITIS: IMPACT ON CLINICAL PRACTICE AND
QUALITY OF CARE
Marwan Bukhari1,2, Preeti Shah3, George Kitas4, Maureen Cox5,
Alan Nye6, Anne O’Brien7, Peter Jones8 and Ify Sargeant9
1
Rheumatology Department, University Hospitals of Morecambe
Bay NHS Foundation Trust, Royal Lancaster Infirmary, Lancaster,
United Kingdom; 2Clinical Sciences, University of Liverpool,
Liverpool, United Kingdom; 3Rheumatology, Trafford General
Hospital, Trafford, United Kingdom; 4Rheumatology, Dudley group
of hospitals NHS trust, Dudley, United Kingdom; 5Rheumatology,
Nuffield Orthopaedic Centre, Oxford, United Kingdom;
6
Rheumatology, Pennine MSK partnership, Oldham,
United Kingdom; 7School of Health and Rehabilitation, Keele
University, Keele, United Kingdom; 8Statistics, Keele University,
Keele, United Kingdom; 9Communications, ismedica Ltd, Wrinehill,
United Kingdom
Background: The 2010 White Paper Equity and excellence: Liberating
the NHS, highlights the need to measure clinically-relevant outcomes
that are important to patients (pts) to assess quality of care. RA has
now been chosen as a disease area by DoH to assess quality
standards. Commissioning for Quality in Rheumatoid Arthritis (CQRA)
has developed commissioning metrics for RA, based on NICE
guidance, in order to drive implementation of best practice in RA. A
pilot study of 86 pts in 2010 indicated that the metrics are easily
administered in existing rheumatology units. We report results of a
follow-up study one year later.
Methods: Four units (Dudley Group NHS FT, Royal Lancaster
Hospital, Trafford General Hospital and the Nuffield Orthopaedic
Centre Oxford) contributed consecutive pts to the follow-up 2011
study and administered the audit tool. Clinical management was
scrutinized in both established and recent onset (disease duration 2
years) RA pts. Questionnaire responses were collated and analysed.
Results: 118 pts were included in the study; the majority of pts were
>61 yrs. Thirty-seven (31%) had recent onset RA and 81 (69%)
established RA, of whom 25 (31%) had disease duration of >10 years.
For recent onset pts: 24/34 pts (71%) had DAS28>2.6. Of these, 88%
were seen every 4-6 weeks and DAS28 score assessed at every visit in
88%; 71% had rapid escalation of treatment until clinical remission or
DAS282.6 was achieved. Compared to 2010, improvement in DAS28
monitoring was noted (88% vs. 74%). For established pts: 27/78 pts
(35%) had high/moderate disease activity according to DAS28, of
these 37% had regular DAS28 assessment every 4-6 weeks; 45/57 pts
(80%) had low disease activity (DAS28<3.2). Of these, 67% had
DAS28 assessment every 3-6 months. 71% of eligible established pts
had treatment modification until sustained low disease activity or
remission was achieved; and 16% received biologics, of whom 92%
iii131
had an adequate response within 6 months. Compared to 2010,
improvement in tight control was noted (71% vs. 45%). For both recent
onset and established RA pts at annual review: disease damage was
measured in 83% of eligible pts; co-morbidities assessed in 86%;
complications assessed in 61%; cross referral within the multidisciplinary team assessed in 90%; need for surgical referral assessed
in 72%; and the impact of RA on pts assessed in 72%. Compared to
2010, improvements were noted in 4 of 6 annual review categories. We
will present and compare full results from 2010 and 2011 data.
Conclusions: The CQRA metrics provide an effective tool for
monitoring RA service quality for commissioners and clinicians and
identifying areas for improvement and highlight how data can be used
to drive change. Implementation of the metrics can impact and
facilitate improvement of quality of care as assessed by measuring
alignment of actual clinical practice to best practice as defined and
advocated by NICE.
Disclosure statement: M.B. received honoraria from UCB, Roche,
Pfizer, Merck, Menarini and Proctor and Gamble, funding for computer
software from Roche and Pfizer, attended conferences held by UCB,
Roche, Pfizer, Merck and Eli Lilly, and attended meetings at Servier.
I.S. is a freelance medical writer employed by Roche. All other authors
have declared no conflicts of interest.
212. THE EFFECTIVENESS OF PRACTITIONER-BASED
COMPLEMENTARY AND ALTERNATIVE THERAPIES IN
THE MANAGEMENT OF RHEUMATOID ARTHRITIS
Gareth T. Jones1, Priya Paudyal1,2, Hugh MacPherson3, Julius Sim4,
Mike Doherty5, Edzard Ernst2, Margaret Fisken1, George Lewith6,
Jane Tadman7 and Gary J. Macfarlane1
1
Aberdeen Musculoskeletal Research Group (Epidemiology),
University of Aberdeen, Aberdeen, United Kingdom; 2Peninsula
College of Medicine & Dentistry, Universities of Exeter and Plymouth,
Plymouth, United Kingdom; 3Department of Health Sciences,
University of York, York, United Kingdom; 4School of Health and
Rehabilitation, Keele University, Keele, United Kingdom; 5Arthritis
Research UK Pain Centre, University of Nottingham, Nottingham,
United Kingdom; 6Community Clinical Sciences, University of
Southampton, Southampton, United Kingdom; 7Press Office,
Arthritis Research UK, Chesterfield, United Kingdom
Background: Over £½billion is spent per annum on complementary
and alternative (CAM) treatments in the UK and 80% of all CAM
consultations relate to rheumatological problems. A recent review
examined the role of CAM treatments taken orally or applied topically
in the treatment of rheumatoid arthritis (RA). The aim of the current
review was to evaluate the evidence regarding practitioner-based
CAM treatments in the treatment of RA.
Methods: Several databases were searched, to May 2011, including
Medline, Embase, Cochrane Register of Controlled Trials, and AMED
(Allied and Complementary Medicine). The search combined 77 names
of practitioner-based CAM treatments commonly used in rheumatic
diseases, plus RA, and was limited to randomized trials or systematic
reviews published in English. The titles/abstracts of identified papers
were screened by two reviewers to identify those for full-text review.
Disagreements were resolved by consensus, and the bibliographies of
eligible articles were checked to identify any additional papers. Data
were extracted by a single reviewer, and checked by a second, and
the Jadad score was used to assess methodological quality of the
trials (0 ¼ poor; 5 ¼ high quality).
Results: From 713 articles, 12 trials were identified, examining seven
therapies. The effectiveness of meditation has been tested in two trials
(both Jadad ¼ 4) among a total of 207 patients. Neither demonstrated
an improvement in pain or disability immediately after treatment,
although one showed improvements in pain coping effectiveness and
psychological distress at six months. Acupuncture was examined in
four trials (median Jadad ¼ 4), with the number of patients ranging from
36 to 64, and treatment varying from five to 20 sessions. One trial that
compared acupuncture against autogenic training reported positive
findings in terms of pain and disability. However, all three trials
comparing true with sham acupuncture reported no significant
difference in pain reduction between groups. Finally, one trial each
examined the effectiveness of healing therapy (Jadad ¼ 3), progressive
muscle relaxation (Jadad ¼ 3), static magnets (Jadad ¼ 4) and Tai Chi
(Jadad ¼ 4). In each instance, either no improvements were found in
pain, function or other relevant outcomes (in either group), or, where
some improvements were seen, there were no significant differences
between treatment groups.
Conclusions: The major limitation in reviewing the evidence for
practitioner-based CAM treatments in the treatment of RA is the
paucity of RCTs. The available evidence does not suggest they are
effective but, the lack of trials, means we cannot reach firm
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
disease duration was 8.9 (7.6) y for RTX and 7.6 (6.6) y for alternative
TNFi patients; mean (SD) duration of all previous TNFi therapy was
25.9 (26.2) and 23.5 (24.8) mo, respectively. A higher proportion of
patients in the RTX group compared with the alternative TNFi group
were seropositive (rheumatoid factor: 83.0% vs 69.7%; p < 0.0001;
anti-citrullinated peptide antibody: 69.1% vs 63.2%; p ¼ NS). At the
start of the new therapy, mean (SD) DAS28-ESR was significantly
higher (p ¼ 0.0005) in the RTX group [5.4 (1.3)] vs the alternative TNFi
group [5.0 (1.4)]. At 6 months, significantly greater decreases in
DAS28-ESR were observed in RTX vs alternative TNFi patients: mean
improvement at 6 months 1.6 vs 1.2 (p ¼ 0.047). A significantly
greater decrease in ESR (-15.4 vs 9.7; p ¼ 0.022) was also observed
in the RTX vs the alternative TNFi group. Numerically better results
were also seen for the other DAS28 components (joint counts, global
disease activity assessment).
Conclusions: These interim data from the SWITCH-RA study indicate
that in patients with RA who discontinued a first TNFi, significantly
better 6-month efficacy results (as measured by DAS28-ESR) were
achieved in those who switched to RTX therapy compared with
patients who switched to an alternative TNFi.
Disclosure statement: D.C. received a research grant and speaker
fees from Roche. M.D. is an employee of F Hoffmann-La Roche. P.E.
provided expert advice of Pfizer and Merck, and received consulting
fees from Abbott, BMS and Roche. A.F. received consultancy fees
from, and is a member of the speakers bureau of, Roche. E.G. is an
employee of Quintiles. J.G. received honoraria from Abbott, BMS,
MSD, Pfizer and Roche. R.M. received a research grant from Roche.
C.M. is an employee of Hoffmann-La Roche. P.S. received research
grants from Roche, Pfizer, UCB and Abbott. T.S. is an investigator for
GSK, Novartis, UCB and Medco, and is a member of the advisory
boards of UCB and Abbott. All other authors have declared no
conflicts of interest.
Wednesday 2 May 2012, 10.45 – 11.45
iii132
Wednesday 2 May 2012, 10.45 – 11.45
conclusions. Even in acupuncture, where several high quality trials
exist, the evidence suggests it is no better than sham acupuncture in
terms of pain reduction. In summary, although commonly used
therapies, there is little convincing evidence to support the use of
practitioner-based CAM treatments in the treatment of RA.
Disclosure statement: All authors have declared no conflicts of
interest.
213. POOLED ANALYSIS OF THE RISK OF SERIOUS
INFECTIONS AND OPPORTUNISTIC INFECTIONS IN CLINICAL
TRIALS OF CERTOLIZUMAB PEGOL FOR RHEUMATOID
ARTHRITIS
Background: Certolizumab pegol (CZP) is indicated for the treatment
of rheumatoid arthritis (RA) in the US and in Europe: in the US, it is also
indicated for treating Crohn’s disease (CD). Much data on the safety of
CZP has been collected in both indications, from real-life practice and
clinical trials. We present an update of the CZP safety profile (adverse
events (AEs) and serious AEs) focusing on infections, serious infections
(SI) and opportunistic infections (OI).
Methods: A pooled analysis of RA trial data available up to November
2010 was performed. This covered 3,397 patients (almost 40% from
Central and Eastern Europe), with 8,658 patient-years (PY) of CZP
exposure. Other trials involving >5,000 patients across indications
were not included in the pooled analysis. Data from drug monitoring
programmes were also excluded, as these programmes are known to
under-report AEs. However, all SIs reported up to December 31st 2010
were reviewed from all sources in both CD and RA.
Results: For RA, of 487 SIs, 76 OIs were recorded in the pooled trials
(52 cases of tuberculosis (TB), 11 cases of herpes, 2 cases each of
legionellosis, salmonellosis, aspergillosis and histoplasmosis, and 1
case each of nocardiosis, pseudomonas, EBV and other fungal
infections).
In total, 40 OI were identified in other trials not included in the
pooled analysis (20 cases of TB, 8 of herpes, 3 cases each of candida,
and pneumonia, and 1 case each of salmonella, staphylococcus,
CMV, EBV, aspergillus, infectious gastroenteritis and other fungal
infections).
In total, 30 OI were spontaneously reported in real life (8 in RA
patients, 18 in CD patients and 4 in an unreported disease area).These
included 12 cases of herpes, 4 of TB, 3 of candidiasis*, 2 each of
coccidiosis*, histoplasmosis*, legionella, CMV* and 1 case each of
salmonella, non TB mycobacterium and EBV. (*indicates OI was
reported in CD).
Conclusions: The profile of AEs, serious AEs, SIs and OIs for CZP was
similar to that reported for other anti-TNFs. The incidence of SIs was
comparable to that recorded for anti-TNF treatment (with adalimumab,
etanercept or infliximab) in the BSR-BR database (4.2/100 PY). No new
infectious safety signals were detected. The incidence of TB was
notable in the population that contained a high proportion of Central
and Eastern European patients, but is comparable to that recorded for
adalimumab in the ReAct study (0.50/ 100 PY), and is in a similar range
to that recorded for other anti-TNFs in the BSR-BR database.
TABLE 1 Incidence rates of AEs in the pooled RA trials analysis for the ‘‘All CZP
Doses’’ group
Incidence in RA (/100 PY)
AEs
Serious AEs
Infections
SIs
TB
57.29
13.75
38.61
4.43
0.54
Disclosure statement: C.A. is an employee of UCB. P.B. received a
research grant from UCB. M.D. is an employee of UCB. X.M. received
research grants from UCB, Pfizer, Roche and Human Genome
Science, and honoraria from UCB, Pfizer, Roche, BMS, GSK and
Pfizer. I.T. is an employee of UCB. B.V. is an employee of UCB.
214. KEY PHARMACOLOGICAL PARAMETERS SUPPORT
MONTHLY DOSING FOR GOLIMUMAB
Honghui Zhou1, Ann Cai1, Eilyn Lacy1, Jonathan Kay2, Ed Keystone3,
Eric Matteson4, Chuanpu Hu1, Elizabeth Hsia1,5, Mittie Doyle1,5,
Mahboob Rahman1 and David Shealy1
1
Immunology, Janssen Research & Development, Inc, Malvern,
Pennsylvania, United States of America; 2Rheumatology Center,
UMass Memorial Medical Center, Worcester, Massachusetts, United
States of America; 3Rheumatology, University of Toronto, Toronto,
Ontario, Canada; 4Rheumatology, Mayo Clinic, Rochester, Ontario,
Canada; 5Rheumatology, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania, United States of America
Background: To compare the molecular characteristics and clinical
pharmacology of SC golimumab (GLM) and adalimumab (ADA), two
human anti-TNFa antibodies with similar half-lives but different dosing
frequencies.
Methods: Affinity to soluble TNFa was measured by surface plasmon
resonance. Evaluation of in vitro neutralization efficiency (NE) was
accomplished using bioassays for TNFa-induced cytotoxicity on a
human rhabdomyosarcoma cell line (KYM-1D4) and E-selectin
expression by primary human umbilical vein endothelial cells. A PK/
PD model was developed using serum GLM concentrations (conc) and
ACR20/50/70 results from GO-FORWARD (Ph 3 trial) using the
MTX þ PBO, MTX þ GLM 50 mg, and MTX þ GLM 100 mg grps.
Mixed-effect logistic regression was used with a latent variable
approach, in conjunction with an inhibitory indirect effect model, to
model ACR20/50/70 results simultaneously. The PK/PD model linked
time profiles of GLM conc and ACR20/50/70. Results from a Ph 2
dose-ranging study evaluating efficacy of GLM 50 or 100 mg SC q2 or
4wk in pts with active RA despite MTX are presented. The GLM 50 and
100 mg q2 wk grps are combined into a (q2 wk) grp; GLM 50 and
100 mg q4 wk grps are combined into another (q4 wk) grp to assess
the relative clinical efficacy of q2 and q4 wk dosing. Primary endpoint
was ACR20 at wk 16. ACR20 is presented over time from wks 2-16.
Results: Affinity (mean; range) of GLM for TNFa (18pM; 9-27 pM) was
significantly greater than ADA (127 pM; 99-154; p ¼ 0.018).
Neutralization efficiency (NE) was compared as moles of antibody
required to achieve 50% inhibition/mole of TNFa. NE for GLM in the
cytotoxicity assay was 22.1 vs 124 for ADA (p < 0.001); in the Eselectin assay, NE for GLM was 1.32 vs 4.32 for ADA (p ¼ 0.008). A 3 to
6 fold higher conc of ADA was necessary to neutralize the same level
of TNFa as GLM in vitro. The EC50 value (in vivo potency) for GLM by
the current exposure-response model, using GO-FORWARD data,
was estimated to be 454 296 ng/mL, which is smaller than the
reported EC50 for ADA by PK/PD analysis (810 370 ng/mL). Although
analysed by different PK/PD methods, this appears consistent with the
in vitro potency comparison. In the Ph 2 GLM dose ranging study, the
proportions of pts who achieved ACR 20 at wk 16 (primary analysis)
were 58.0% (p ¼ 0.045) and 64.7% (p ¼ 0.008) for GLM q4wk þ MTX
(n ¼ 69) and GLM q2wk þ MTX (n ¼ 68) grps, respectively (vs 37.1% for
the PBO þ MTX grp [n ¼ 35]). Comparable efficacy was seen in q4 wk
and q2 wk dosing.
Conclusions: Compared with ADA, GLM demonstrates greater affinity
to TNFa and capacity to neutralize TNFa, in in vitro assays, and lower
EC50, in PK/PD modeling. These data suggest that similar conc of
GLM would maintain efficacy for longer duration than those of ADA
and allow less frequent dosing, despite similar half-lives. A Ph2 dose
ranging study also supports monthly dosing of GLM by demonstrating
comparable clinical efficacy with q2 wk and q4 wk dosing.
Disclosure statement: A.C. is an employee of Janssen. M.D. is an
employee of Janssen. E.H. is an employee of Janssen. C.H. is an
employee of Janssen. J.K. is an investigator for Janssen. E.K., is
an investigator for Janssen. E.L. is an employee of Janssen. E.M. is an
investigator for Janssen. M.R. is a former employee of Janssen. H.Z. is
an employee of Janssen. D.S. is an employee of Janssen. H.Z. is an
employee of Janssen.
215. COMBINATION ANTI-RHEUMATIC DRUGS IN EARLY
RHEUMATOID ARTHRITIS: COMPARISON OF FINDINGS IN
TWO RANDOMIZED CONTROLLED TRIALS
David L. Scott1, Fowzia Ibrahim1, Hanan Abozaid1, Ernest Choy1,
Andrew Hassell2, Michael Plant3, Selwyn Richards4, David Walker5,
Gemma Simpson1 and Anna Kowalczyk1
1
Rheumatology, King’s College London, London, United Kingdom;
2
Rheumatology, Haywood Hospital, Stoke-on-Trent,
United Kingdom; 3Rheumatology, James Cook University Hospital,
Middlesbrough, United Kingdom; 4Rheumatology, Poole Hospital,
Poole, United Kingdom; 5Rheumatology, Freeman Hospital,
Newcastle upon Tyne, United Kingdom
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
X. Mariette1, P. Bertin2, C. Arendt3, I. Terpstra4, B. VanLunen5 and
M. de Longueville6
1
Service de Rhumatologie, Universite´ Paris-Sud, Hoˆpital Biceˆtre,
Le Kremlin-Biceˆtre Paris, France; 2Service de Rhumatologie, C.H.U.
Dupuytren, Limoges, France; 3Clinical Development, UCB Pharma,
Brussels, Belgium; 4GCSP Drug Safety, UCB Pharma, Brussels,
Belgium; 5Global Biostatistics, UCB BioSciences Inc, Research
Triangle Par, North Carolina, United States of America; 6Global
Medical Affairs, UCB Pharma, Brussels, Belgium
POSTER VIEWING II
POSTER VIEWING II
216. COMPLIANCE WITH NICE CLINICAL GUIDELINE 79
IN THE MANAGEMENT OF PATIENTS WITH RHEUMATOID
ARTHRITIS IN 5 NHS TRUSTS IN ENGLAND
Peter Prouse1, Andrew Brown2, Mano George3, Namita Kumar4,
Kirsten Mackay5 and Samantha Marshall6
1
Department of Rheumatology, Basingstoke and North Hampshire
NHS Foundation Trust, Basingstoke, United Kingdom; 2Department
of Rheumatology, York Teaching Hospital NHS Foundation Trust,
York, United Kingdom; 3Department of Rheumatology, Wirral
University Teaching Hospital NHS Foundation Trust, Wirral,
United Kingdom; 4Department of Rheumatology, County Durham
and Darlington NHS Foundation Trust, Durham, United Kingdom;
5
Department of Rheumatology, South Devon Healthcare NHS
Foundation Trust, Torbay, United Kingdom; 6pH Associates, Marlow,
United Kingdom
Background: In February 2009, the National Institute for Health and
Clinical Excellence (NICE) issued guidance on the management of
rheumatoid arthritis (RA) focusing primarily on newly diagnosed
patients (CG79).
In view of the considerable burden of RA to individual patients and
society, there was interest in demonstrating how well RA was being
managed.
The objective of the audit was to assess compliance with NICE
CG79 in patients with newly diagnosed RA.
Methods: 6-12 months of routine management data were collected
retrospectively from medical notes of patients newly diagnosed with
RA between May 2009 and December 2010 in 5 NHS specialist
Rheumatology centres between November 2010 and June 2011. Data
were recorded anonymously, according to the study protocol. Local
iii133
NHS management approval was gained for release of data for pooled
analysis and reporting.
Results: Data were collected on 121 newly diagnosed RA patients,
68% female, mean age 58.75 years on referral.
Median time from onset of persistent symptoms to referral was
4 months (range 2.6 to 83.2 incl. one patient under the care
of rheumatology prior to symptom onset), from referral to 1st
rheumatology appointment was 4.8 weeks (range 0-20) and from 1st
rheumatology visit to initiation of DMARD based therapy was 55.0
days (range 0 - 870).
Median delay from onset of persistent symptoms to DMARD
therapy was 8 months (range 1-87) with 24% of patients being referred
to secondary care within 3 months of symptom onset as suggested by
NICE.
1
7% of patients with newly diagnosed RA were commenced
on combination DMARDs, in 1 patient this was within 3 months of
symptom onset. A further 41% were commenced on DMARD
monotherapy, of these 10% were within 3 months of symptom onset.
1
% of patients had monthly DAS28 scores and 2% had their CRP
measured monthly as recommended by NICE.
60% of patients received written information about their condition
and 66% about their treatment. 9% had a named member of the
multidisciplinary team responsible for their care.
Conclusions: NICE recommendations for the management of RA are
not being achieved in this sample. There is an unacceptable delay in
referral to specialist care which has not improved over time despite
evidence to support early treatment. The causes for this are likely to be
multifactorial and could worsen in the current NHS, where GPs are not
always prioritizing referral of patients with musculoskeletal (MSK)
conditions to secondary care.
The results also suggest a reluctance to follow guidance in terms of
triple therapy; an area of debate in the clinical and scientific
community.
Less than 2% of people are managed by tight control as advised by
NICE, which is likely to be due to lack of capacity in secondary care.
In order to achieve the NICE standards, more ambitious initiatives
between primary and secondary care and prioritization of MSK
conditions by the DOH are necessary.
Disclosure statement: A.B. received funding for audit work from
Abbott. M.G. received funding for audit work from Abbott. N.K.
received funding for audit work from Abbott. K.M. received funding for
audit work from Abbott. S.M. received funding for facilitation of audit
work from Abbott. P.P. received funding for audit work from Abbott.
217. EFFICACY, SAFETY AND PHARMACOKINETICS OF
SUBCUTANEOUS ABATACEPT IN PATIENTS WITH
RHEUMATOID ARTHRITIS, WITH OR WITHOUT AN
INTRAVENOUS LOADING DOSE
Peter T. Nash1, Charles L. Ludivico2, Ingrid Delaet3, Keqin Qi4,
Bindu Murthy3, Michael Corbo5 and Jeffrey L. Kaine6
1
Rheumatology Research Unit, University of Queensland, Brisbane,
Queensland, Australia; 2Rheumatology, East Penn Rheumatology
Associates, Bethlehem, Pennsylvania, United States of America;
3
Global Clinical Research Immunology, Bristol-Myers Squibb,
Princeton, New Jersey, United States of America; 4Global Biometric
Sciences, Bristol-Myers Squibb, Princeton, New Jersey, United
States of America; 5Global Clinical Research, Bristol-Myers Squibb
(at time of study), Princeton, New Jersey, United States of America;
6
Rheumatology, Sarasota Arthritis Center, Sarasota, Florida, United
States of America
Background: Use of IV ABA is well established in pts with RA. Pivotal
trials of SC abatacept MTX have shown efficacy. Some trials
included an IV ABA loading dose to rapidly achieve therapeutic
steady-state drug concentrations (Cminss 10 mg/mL). We evaluated
open-label data from 2 Phase III trials to examine the 3-mth efficacy
and clinical pharmacokinetics (PK) of SC ABA (125 mg/wk), with/
without IV loading, in pts with established biological or non-biological
DMARD-refractory RA.
Methods: In the initial open-label (OL) period of the ALLOW trial, pts
received SC ABA þ MTX, with IV loading on Day 1 (10 mg/kg; SC þ IV
load). In the OL ACCOMPANY trial, pts were stratified to SC
ABA MTX, with no IV load (SC only). Data up to Mth 3 for disease
activity (DAS28-CRP) and physical function (HAQ-DI) were based on
pts with data available (clinically meaningful responses [CMRs] defined
as reductions of 1.2 in DAS28 and 0.3 in HAQ-DI). PK was
assessed for both trials using a validated ELISA to determine ABA
serum trough concentrations (Cmin).
Results: 167 pts entered ALLOW and received SC ABA þ IV load; 100
pts entered ACCOMPANY and received SC only ( MTX). Mean (SD)
baseline demographics were generally similar between studies,
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: Background: The optimal initial treatment of early
rheumatoid arthritis (RA) remains uncertain. One key goal is reducing
x-ray progression and there is strong evidence that combination
therapy using methotrexate helps minimize x-ray progression.
However, the most cost-effective treatment strategy remains uncertain. We have further examined this question in 3 related studies. (a) As
interleukin-1 (IL1) reduces x-ray progression in established RA, we
assessed whether it is effective combined with methotrexate in early
RA. (b) We compared the impact of IL1 inhibition to our previous
published experience with steroid/methotrexate combinations in early
RA. (c) We modelled the data from these studies to identify early
indicators of reduced x-ray progression.
Methods: (a) We studied the impact of IL1 inhibition in a 24-month
multicentre randomized controlled trial (RCT). 159 patients with early
RA (<12 months) were randomized to receive methotrexate (15 mg
target) alone or with 12 months daily subcutaneous anakinra (b) A
previous RCT compared methotrexate (15 mg target) with or without 9
months prednisolone in 224 comparable early RA patients. Clinical and
radiological assessments were made at baseline, 6, 12 and 24 months.
Results: (a) In the 1st RCT both methotrexate and methotrexate/
anakinra significantly reduced disease activity scores (DAS28) by
6 months (mean 2.1 and 2.2); DAS28 did not improve further thereafter.
DAS28 components (including ESR) and disability (HAQ) showed
similar improvements. Methotrexate and methotrexate/anakinra had
identical effects on disease activity measures. Erosive progression
showed a small difference between groups in year 1 (mean change in
Larsen score (SD): methotrexate 4.9 (13.6); methotrexate/anakinra 1.6
(7.9); p ¼ 0.07). Erosive progression over 24 months was similar in both
groups. Intention to treat and completer analyses gave comparable
findings.
(b) In the 2nd RCT steroids/methotrexate significantly reduced
DAS28 and ESR at 6 months compared to methotrexate monotherapy
(p ¼ 0.003 and 0.037) and also significantly reduced radiological
progression (by Larsen score) over 12 and 24 months (p ¼ 0.001 and
0.03). Clinical changes were similar at 12-24 months with steroids/
methotrexate and methotrexate
(c) Regression analysis of 2nd RCT showed ESR and patient global
assessments at 6 months significantly predicted x-ray progression in
year 1 (adjusted analysis showed p ¼ 0.023 and 0.033). Other clinical
assessments (joint counts, pain, HAQ) had no significant impact.
Conclusions: In early RA reducing acute phase indicators like the
ESR is crucial to minimize erosive progression. Though IL1 inhibition
reduces erosive progression in established RA, its impact above that
of methotrexate alone is modest in early RA. Combining short-term
steroids with methotrexate, is affordable, reduces both ESR and
erosive damage and, we suggest, forms a "gold standard" to judge
more expensive treatments.
Disclosure statement: All authors have declared no conflicts of
interest.
Wednesday 2 May 2012, 10.45 – 11.45
iii134
Wednesday 2 May 2012, 10.45 – 11.45
218. EFFICACY AND SAFETY OF CERTOLIZUMAB PEGOL
AFTER INCOMPLETE RESPONSE TO DMARDS IN
RHEUMATOID ARTHRITIS PATIENTS WITH LOW MODERATE
DISEASE ACTIVITY: RESULTS FROM CERTAIN, A PHASE
IIIB STUDY
Paul Emery1, Josef S. Smolen2, W. Samborski3, F. Berenbaum4,
Owen Davies5, J. Ambrugeat5, B. Bennett6 and H. Burkhardt7
1
Academic Unit of Musculoskeletal Disease, University of Leeds,
Leeds, United Kingdom; 2Divisions of Rheumatology and Medicine,
Medical University of Vienna and Hietzing Hospital, Vienna, Austria;
3
Department of Rheumatology, K. Marcinkowski University of
Medical Sciences, Poznan, Poland; 4Department of Rheumatology,
AP-HP St Antoine Hospital, Paris, France; 5UCB, UCB Pharma,
Brussels, Belgium; 6UCB, UCB Pharma, Smyrna, Georgia, United
States of America; 7Division of Rheumatology, Johan Wolfgang
Goethe University, Frankfurt am Main, Germany
Background: There is a need to understand whether treatment with
anti-TNFs can provide therapeutic benefits to RA patients (pts) with
low to moderate disease activity (DA). This study
was conducted to evaluate certolizumab pegol (CZP) in combination with non-biologic DMARDs in pts with low to moderate DA.
Methods: CERTAIN (CERTolizumab pegol in the treatment of RA:
remission INduction and maintenance in pts with low DA) was
designed to enrol pts with low to moderate DA (CDAI >6 and 16)
(NCT00674362). Pts were randomized (1:1) to CZP (400 mg at Wks 0, 2
and 4, then 200 mg every other wk) or placebo (PBO) þ existing
DMARDs. Primary efficacy analysis was % of pts in CDAI remission at
both Wks 20 and 24. Other analyses included DAS28 and SDAI
remission at both Wks 20 and 24, ACR20/50/70 responses and change
from baseline (BL) in HAQ-DI at Wk 24, and safety. CDAI/SDAI/DAS28
remission and ACR responses were assessed using NRI, and HAQ-DI
using LOCF. Pts with CDAI remission (2.8) at Wks 20 and 24 stopped
CZP and were monitored to Wk 52. Here, we report Wk-24 data.
Results: A total of 194 pts were randomized (CZP: n ¼ 96, PBO:
n ¼ 98; mean age 54 y, 80.4% female, mean TJC 3.8, mean SJC 3.3,
mean CRP 7.9 mg/L). Mean RA duration was 4.5 y in CZP pts and 4.7 y
in PBO pts. Mean BL scores were similar between CZP and PBO for
CDAI (13.5 vs 13.3), HAQ-DI (1.1 vs 1.0) and DAS28 (4.50 vs 4.47). At
BL, >90% of pts had moderate DA (CDAI, moderate DA range: >1022). More than twice as many CZP pts had CDAI remission at both
Wks 20 and 24 than PBO pts (18.8% vs 7.1%, p < 0.05). More CZP pts
had DAS28 (19.8% vs 3.1%, p < 0.01) or SDAI remission (14.6% vs
4.1%, p < 0.05) at both Wks 20 and 24. Mean CDAI improved in CZP
pts to 9.4 and deteriorated to 16.5 in PBO pts at Wk 24 (mean change
from BL: 4.20 vs 2.71, p < 0.001). At Wk 24, more CZP pts had CDAI
remission/low DA (63.1% vs 30.4%, p < 0.001) and fewer CZP pts had
moderate/high DA (37.0% vs 69.6%). Despite low BL mean joint
counts, ACR20/50/70 responses at Wk 24 were higher with CZP
(ACR20: 36.5% vs 16.3%, p < 0.01; ACR50: 20.8% vs 8.2%, p < 0.05;
ACR70: 9.4% vs 3.1%, p ¼ NS). CZP pts had greater HAQ-DI
improvements at Wk 24 (mean change from BL: 0.25 vs 0.06,
p < 0.01). CZP was well tolerated with AE and serious AE rates
comparable between CZP and PBO (66.7% vs 66.3%; 4.2% vs 4.1%).
Conclusions: In RA pts with long-standing low moderate DA, addition
of CZP to non-biologic DMARDs increased rates of remission and low
DA and inhibited progression to high DA.
Disclosure statement: J.A. is an employee of UCB. B.B. is an
employee of, and has stock options in, UCB. F.B. received
consultancy fees from UCB. H.B. received consultancy fees from
UCB. O.D. is an employee of, and has stocks, stock options or bond
holdings in, UCB. P.E. received grants/research support and consultancy fees from UCB. W.S. received consultancy fees from UCB.
J.S. received Grants/research support and consultancy fees from
UCB.
219. COMPLIANCE WITH NICE TECHNOLOGY APPRAISALS
TA130 AND TA186 IN THE USE OF TNF-A INHIBITOR THERAPY
IN PATIENTS WITH RHEUMATOID ARTHRITIS IN 5 NHS
TRUSTS IN ENGLAND
Peter Prouse1, Andrew Brown2, Mano George3, Namita Kumar4,
Kirsten Mackay5 and Samantha Marshall6
1
Department of Rheumatology, Basingstoke and North Hampshire
NHS Foundation Trust, Basingstoke, United Kingdom; 2Department
of Rheumatology, York Teaching Hospital NHS Foundation Trust,
York, United Kingdom; 3Department of Rheumatology, Wirral
University Teaching Hospital NHS Foundation Trust, Wirral,
United Kingdom; 4Department of Rheumatology, County Durham
and Darlington NHS Foundation Trust, Durham, United Kingdom;
5
Department of Rheumatology, South Devon Healthcare NHS
Foundation Trust, Torbay, United Kingdom; 6pH Associates, Marlow,
United Kingdom
Background: At the time of audit, there were 2 sets of guidance
relating to the use of TNF-a inhibitors for treatment of severe
rheumatoid arthritis (RA); Technology Appraisal (TA) 130 relating to
adalimumab, etanercept and infliximab and TA186 for certolizumab.
Despite guidance, data from the British Society of Rheumatology
Biologics Register suggested that patients were not receiving TNF-a
inhibitors appropriately and hence the objective of the audit was to
assess whether patients prescribed a TNF-a inhibitor were eligible for
treatment and subsequently managed in line with guidance.
Methods: Routine management data were collected retrospectively
from medical notes in 5 NHS specialist Rheumatology centres from all
patients commenced on a TNF-a inhibitor between May 2008 and April
2011, and included at least 6 months of follow up data. Data were
recorded anonymously, with local NHS management agreement in
place for release of data for pooled analysis and reporting.
Results: 276 patients were included, 71% female, mean age 55.4
years at initiation of TNF-a inhibitor.
Mean DAS28 score (DAS28) pre TNF-a inhibitor was 5.87 (SD 0.85).
192 patients (70%) had 2 DAS28 recorded in the notes prior to
commencing TNF-a inhibitor, of the 84 who did not, 69 patients had
<2 DAS28s and 15 had 2 DAS28s but were not compliant; 12 had
only one DAS28 5.1, two had 2 DAS28s 5.1 but <1 month apart
and one patient had 2 DAS28s both 5.1.
Mean number of DMARDs pre TNF-a inhibitor was 3 (SD 1). 247
patients (89%) had 2 DMARDS incl. 180 (65%) who had 3 for at
least 6 months. Of these 247 patients, in 244 methotrexate was
included in the combination. In 29 (11%) in whom the use of 2
DMARDS was not recorded, 22 received 1 DMARD and in 7 no prior
DMARD was recorded.
Mean time to 1st DAS28 post TNF-a inhibitor initiation was 19
weeks (SD 14, range 1 to 94 weeks). 81% of patients had DAS28
assessed within 6 months. Mean time between DAS28 thereafter was
24 weeks (SD 12, range 4-74 weeks).
Mean change in DAS28 at 6 months was 2.34 (SD 1.35, range
2.04 to 5.59).
16 patients (6%) did not have an improvement in DAS28 1.2
points at 6 months. Of these, 3 stopped treatment, 8 switched to
another biologic agent and 5 continued treatment.
Conclusions: Compliance with NICE TA130/TA186 was demonstrated
to be good in the majority of Trusts involved with this audit.
The record of pre TNF-a inhibitor DAS28 scores was inadequate
from the notes in 25% of patients but may have been recorded
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
although baseline disease was less severe in SC þ IV versus SC only
pts; tender and swollen joints were 14.3 (10.3) and 11.0 (5.7) vs 24.1
(16.2) and 17.2 (12.1), DAS28 was 4.7 (0.9) vs 5.4 (1.4) [n ¼ 98], and
HAQ-DI was 1.3 (0.7) vs 1.4 (0.7) [n ¼ 99]. Mean (SD) disease duration
was 7.5 (8.0) yrs vs 10.1 (11.1) yrs in SC þ IV vs SC-only pts,
respectively. All SC þ IV pts and 81% of SC-only pts had previously
failed MTX; 11% and 23% of pts had previously received biologicals.
Improvements in DAS28 and HAQ-DI were generally comparable with
or without IV load; CMRs were observed in both trials by Mth 2. By Mth
3, mean (SD) DAS28 was 3.2 (1.3) vs 3.8 (1.4) for SC þ IV vs SC only,
respectively, and HAQ-DI was 0.7 (0.7) vs 1.1 (0.7). Mean (SE) changes
in DAS28 from baseline to Mths 1, 2 and 3 were 1.00 (0.07), 1.35
(0.08) and 1.53 (0.10) for SC þ IV and 0.85 (0.11), 1.35 (0.12) and
1.57 (0.14) for SC only. Occurrence of SAEs, including infections,
was similar with or without IV load. PK assessments indicated target
therapeutic Cmin was achieved by Day 15 in 88% of pts in the SC-only
study. Cminss concentrations were achieved by Mth 2 in both trials and
remained consistent to Mth 3.
Conclusions: Similar improvements in clinical efficacy were observed
over the first 3 mths, with or without IV loading. Target PK values
required for efficacy were achieved in both regimens, and the majority
of pts achieved therapeutic abatacept concentrations by Day 15
without IV loading. These data, although a non-comparative crossstudy assessment, support the hypothesis that IV loading may not be
needed to achieve desired efficacy with SC abatacept.
Disclosure statement: M.C. is an employee of, and holds stock,
stock options or bond holdings in, Bristol-Myers Squibb. I.D. is an
employee of, and holds stock, stock options or bond holdings in,
Bristol-Myers Squibb. J.K. received research grants from BristolMyers Squibb, and is a member of the speakers bureaus of BristolMyers Squibb, Amgen, Novartis and UCB. B.M. is an employee of
Bristol-Myers Squibb. P.N. received consultancy fees, research grants
and honoraria from Bristol-Myers Squibb, and is a member of the
speakers bureau of Bristol-Myers Squibb. K.Q. is an employee of
Bristol-Myers Squibb. All other authors have declared no conflicts of
interest.
POSTER VIEWING II
POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
elsewhere in funding application forms and highlights the need for
adequate staffing levels to collect and maintain this data for robust
record keeping.
Regular monitoring of response to treatment occurred in accordance with NICE guidance, however, there was a wide variation in the
interval between assessments as recorded in the notes.
Disclosure statement: A.B. received funding support for audit work
from Abbott. M.G. received funding support for audit work from
Abbott. N.K. received funding support for audit work from Abbott. K.M.
received funding support for audit work from Abbott. S.M. received
funding support for facilitation of audit work from Abbott. P.P. received
funding support for audit work from Abbott.
220. TOCILIZUMAB AS MONOTHERAPY OR WITH ADD-ON
DISEASE-MODIFYING DRUGS IN RHEUMATOID ARTHRITIS
PATIENTS WITH INADEQUATE RESPONSE TO PREVIOUS
TREATMENTS
Background: Combination therapy with a biologic agent plus a
disease-modifying antirheumatic drug (DMARD) is an established
treatment approach in rheumatoid arthritis (RA). In some patients(pts),
such as those intolerant to methotrexate(MTX), combination therapy
may be inappropriate. In the AMBITION trial, tocilizumab(TCZ)
monotherapy showed significantly superior efficacy compared with
MTX alone in pts who had not been exposed to or who never failed
MTX. However, there are limited data directly comparing TCZ
monotherapy vs TCZ plus add-on DMARDs. The objective of this
analysis was to compare safety & efficacy of TCZ monotherapy vs TCZ
plus DMARDs using data from the ACT-SURE study.
Methods: ACT-SURE was a phase 3b, openlabel, singlearm, 6mth
study in pts with inadequate responses to DMARDs(DMARD-IR) or
tumour necrosis factor (TNF) inhibitors (TNF-IR). Pts received TCZ
8 mg/kg every 4wks, alone or in combination with 1 or more DMARDs
at the investigator’s discretion.
Results: Of 1681 pts in the safety & intent-to-treat populations,
14%(n ¼ 239)received TCZ monotherapy. Of monotherapy pts, 72%
were TNF-IR. 37% of pts with add-on DMARDs were TNF-IR, & 22% of
pts with add-on DMARDs received >1 DMARD. The most commonly
used DMARD was MTX (79% of DMARD pts, of whom 74% had a
weekly dose >10 mg & 47% >20 mg), followed by hydroxychloroquine
(17%), leflunomide (13%), & sulphasalazine (13%). Baseline Disease
Activity Score in 28 joints (DAS28) was similar in both gps (6.2, 5.9).
Safety in monotherapy/add-on DMARDs: treatment withdrawal:5%/
5%;adverse events(AE):82%/77%;serious AE (SAE):8%/8%;AEs leading to withdrawal:5%/5%;infection: 38%/35%;serious infection(most
common SAE):2%/2%;grade 3 neutrophil decrease on at least 1 time
point:1.7%/3.3% (grade 4 decreases;only 1 case in add-on DMARDs,
0.1%); ALT elevation >60U/L at any time point: 6%/9%; AST elevation
>50U/L at any time point: 1.7%/2.4%. At wk24, efficacy end points
were comparable between gps.
Conclusions: Monotherapy with TCZ was highly efficacious at wk24 &
TCZ plus DMARDs provided similar results. Study results from an
almost-real-world setting suggesting that TCZ may be an appropriate
treatment for pts who cannot tolerate MTX. The safety profile was
similar for both gps.
TABLE 1.
Week 24 results, n/n (%)
TCZ monotherapy TCZ þ DMARDs
EULAR good þ moderate response 196/239 (82.0)
ACR50 response
104/239 (43.5)
ACR70 response
57/239 (23.8)
HAQ-DI reductionfrom
143/209 (68.4)
baseline 0.22
DAS28 < 2.6
102/205 (49.8)
CDAI remission
42/205 (20.0)
SDAI remission
44/205 (21.5)
P
1206/1442(83.6)
680/1442 (47.2)
386/1442 (26.8)
912/1242 (73.4)
0.65
0.80
0.76
0.037
724/1250 (57.9)
231/1243 (18.6)
260/1218 (21.3)
0.70
0.18
0.31
p values are for the test of the ‘‘TCZ monotherapy ¼ TCZ þ DMARDs hypothesis’’
using logistic or linear regression models adjusted for previous treatment
(DMARD-IR/TNF-IR) and baseline DAS28, CDAI, or SDAI. n/n ¼ pts who
responded/evaluable pts at week 24.
Disclosure statement: All authors have declared no conflicts of
interest.
221. A RETROSPECTIVE STUDY OF THE EFFECTS OF
SWITCHING FROM ORAL TO SUBCUTANEOUS
METHOTREXATE: THE METHOTREXATE EVALUATION OF
NORWICH TREATMENT OUTCOMES IN RHEUMATOID
ARTHRITIS (MENTOR) STUDY
David G I. Scott1, Pearl Claydon1, Corrinne Ellis1 and Scot Buchan2
Rheumatology, Norfolk and Norwich University Hospital, Norwich,
United Kingdom; 2Strategen Ltd, Basingstoke, United Kingdom
1
Background: MTX is standard first-line therapy for the treatment of
rheumatoid arthritis (RA)1 with the majority of patients receiving oral
therapy. Many patients, however, fail oral MTX either due to tolerability
issues or a lack of efficacy, which then leads to drug switching or
addition of other disease-modifying anti-rheumatic drugs (DMARDs) or
a biologic. Consequently, many patients may not have derived the full
benefits of MTX therapy since data suggest the use of SC MTX may
offer clinical advantages over oral MTX in both tolerability and efficacy
parameters.2 The MENTOR audit was set up to provide data on the
use of SC MTX in patients who had ‘failed’ oral MTX with the intention
of increasing the limited evidence base on its use by reviewing all SC
MTX treated patients in the Norwich and Norfolk University Hospital.
Methods: A retrospective medical record review of all patients with RA
who were switched from oral to SC MTX was conducted. Only patients
for whom complete records were available for a minimum of 12
months before and 6 months after the switch of formulation were
included. The objective was to evaluate the clinical outcomes following
a change in therapy from oral to SC MTX in approximately 200 patients
treated for RA.
Results: A total of 198 RA patients’ records have been analysed (51
men, 147 women). Their average age at RA diagnosis was 47 years,
with an average time to failure of oral MTX of 8.9 years for women and
12.9 years for men. The average MTX dose at failure was 17.8 mg.
Failure was due to side-effects (41.6%), lack of efficacy (67.7%), or
both. At failure, 27% of oral MTX patients were receiving other
concomitant DMARD therapy. Following switch to SC MTX, 76.2% of
women and 84.3% of men continued on MTX therapy for at least 6
months. Of those who discontinued, 56% were for tolerability reasons,
with only 14% discontinuation due to a stated lack of efficacy.
Conclusions: Findings from the MENTOR study demonstrate that SC
MTX offers improved tolerability and efficacy over oral therapy, even in
oral failure patients, with high patient continuation throughout the
study period. Significant numbers of patients therefore are able to
continue to benefit from MTX therapy after oral failure without the need
to introduce alternative DMARD or biologic therapy. These results
have both clinical and economic implications for patient management
following oral MTX failure.
Disclosure statement: All authors have declared no conflicts of
interest.
References
1. National Collaborating Centre for Chronic Conditions. Rheumatoid
arthritis clinical guideline for management and treatment in adults.
London: Royal College of Physicians, February 2009.
2. Braun J, Ka¨stner P, Flaxenberg P et al. Comparison of the clinical
efficacy and safety of subcutaneous versus oral administration of
methotrexate in patients with active rheumatoid arthritis. Arthritis
Rheum 2008;58:73–81.
222. RAPID REDUCTIONS IN FATIGUE AND SLEEP
PROBLEMS AND CORRELATION WITH IMPROVEMENTS IN
PATIENT-REPORTED OUTCOMES IN PATIENTS WITH ACTIVE
RHEUMATOID ARTHRITIS TREATED WITH CERTOLIZUMAB
PEGOL IN THE REALISTIC 12-WEEK PHASE IIIB
RANDOMIZED CONTROLLED STUDY
Janet Pope1, Roy Fleischmann2, Maxime Dougados3,
Clifton O. Bingham4, Elena M. Massarotti5, J. Wollenhaupt6,
B. Duncan7, Geoffroy Coteur8 and Michael Weinblatt5
1
Division of Rheumatology, University of Western Ontario, London,
Ontario, Canada; Metroplex Clinical Research Center, University of
Texas/Southwestern Medical Center, Dallas, Texas, United States of
America; 3Department of Rheumatology, Rene´ Descartes University,
Paris, France; 4Divisions of Rheumatology and Allergy, Johns
Hopkins University, Baltimore, Maryland, United States of America;
5
Division of Rheumatology, Brigham and Women’s Hospital, Boston,
Massachusetts, United States of America; 6Department of
Rheumatology, Klinikum Eilbek, Hamburg, Germany; 7UCB, UCB
Pharma, Raleigh, North Carolina, United States of America; 8UCB,
UCB Pharma, Brussels, Belgium
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Vivian Bykerk1, Andrew J. Ostor2, Jose´ Roma´n Ivorra3,
Jurgen Wollenhaupt4, Andrea Stancati5, Corrado Bernasconi5 and
Jean Sibilia6
1
Rheumatology, Brigham & Women’s Hospital, Boston,
Massachusetts, United States of America; 2Rheumatology, University
of Cambridge, Cambridge, United Kingdom; 3Rheumatology,
Hospital Universitario La Fe, Valencia, Spain; 4Rheumatology, Scho¨n
Klinik, Hamburg, Germany; 5Roche, Roche, Basel, Switzerland;
6
Rheumatology, CHU Hautepierre, Strasbourg, France
iii135
iii136
Wednesday 2 May 2012, 10.45 – 11.45
POSTER VIEWING II
TABLE 1.
Wk2
CZP
Wk6
Control
PRO, Mean change from BL
FAS
1.1
0.2c
MOS-SPI
NA
NA
Pain VAS
15.3
2.8c
PtGA
14.7
2.5c
a
using specific measures. The Health Assessment Questionnaire (HAQ)
has been widely utilized to reflect overall functional status but is not
specific to hand function and has a number of limitations including lack
of sensitivity to subtle changes in function. The Michigan Hand
Outcomes Questionnaire (MHQ), a 37-item questionnaire with 6
domains: function, activities of daily living (ADL), pain, work, aesthetics
and satisfaction has been shown recently to be a reliable and sensitive
measure of hand function which is validated for use in RA patients.
Methods: 16 patients with RA were assessed before and at 3 months
after starting treatment with anti-TNF. The MHQ was completed by
patients at baseline and again at 3 months after treatment initiation and
treatment response were assessed by DAS28 score. Data from each
domain of the MHQ were analysed by comparing baseline and
3 months post treatment using Student’s paired t-test. Correlations
between MHQ scores and DAS28 scores were assessed using
Spearman rank.
Results: The cohort comprised 16 RA patients, 12 females and 4
males, mean age 55.8 years. Mean DAS28 score pre-treatment was
5.29 which reduced to 3.62 at 3 months. There was a significant
improvement in overall MHQ score (p ¼ 0.0038) 3 months after
treatment initiation compared to baseline. MHQ sub-scores of right
and left hand function, work, right and left hand pain and satisfaction at
baseline compared to 3 months post-treatment also showed significant improvement. There was a significant correlation (r ¼ 0.82,
p < 0.0001) between improvement in overall MHQ score and change in
DAS28 score from baseline to 3 months after starting treatment.
Conclusions: Treatment with anti-TNF in our cohort of 16 patients
with RA significantly improved hand function as measured by MHQ
within 3 months of commencing treatment. Interestingly improvement
of hand function in this group correlated with overall improvement in
their inflammatory status as shown by the DAS28 score.
The MHQ is a useful tool for measuring aspects of treatment
outcome that have not been routinely recorded previously. The MHQ is
easy to administer and can identify change within 3 months. It could be
used clinically alongside other widely used measures to monitor
treatment response but importantly it focuses specifically on RA hand
function which other tools do not assess and addresses issues that are
important to patients which impact on their daily life.
Disclosure statement: All authors have declared no conflicts of
interest.
Wk12
CZP
Control
CZP
Control
1.3
7.6
18.4
17.9
0.5c
4.8a
7.9c
7.5c
1.3
7.6
21.2
20.4
0.5c
4.2b
7.8c
7.6c
p < 0.05, bp < 0.01, cp < 0.001 CZP vs Ctrl, NA ¼ not assessed
Disclosure statement: C.B. received research grants and consultancy fees from UCB. G.C. is an employee of UCB. M.D. received
research grants and consultancy fees from UCB. B.D., UCB - UCB
Pharma employee. R.F. received research grants and consultancy fees
from UCB. E.M. received consultancy fees from Merck-Medco, UCB,
Ampimmune, Constellation, Human Genome Sciences and Wachovia,
honoraria from American College of Rheumatology, and is an
investigator for Bristol-Myers Squibb and Roche. J.P. received
research grants and consultancy fees from UCB, Abbott, Actelion,
Amgen, Astra Zenica, BMS, Genetech, GSK, J&J, MedImmune,
Merck, Novartis, Pfizer, Roche, Sanofi, Sorono, Teva and United
Therapeutics. M.W. received research grants from Abbott and UCB,
and consultancy fees from Abbott, UCB, Amgen, Centocor and Pfizer.
J.W. received consultancy fees from UCB, and is a member of the
speakers bureau of UCB.
223. ANTI-TNF THERAPY IMPROVES HAND FUNCTION IN
RHEUMATOID ARTHRITIS WITHIN 3 MONTHS
Dobrina Hull1, Catherine Ball1 and Sonya Abraham2
1
Kennedy Institute of Rheumatology, University of Oxford, London,
United Kingdom; 2Department of Medicine, Imperial College,
London, United Kingdom
Background: Rheumatoid arthritis (RA) is a chronic inflammatory
arthritis affecting 1% of the population worldwide. It is estimated that
hands and wrists are affected in 80-90% of patients with RA, resulting
in pain and reduced ability to use the hands for everyday activities thus
impacting on quality of life. Anti-TNF therapy has revolutionized RA
treatment but its effect on hand function has not been recorded to date
224. A NEW APPROACH WITHIN PERSUASIVE DESIGN
THEORY TO IMPROVE PATIENT ENGAGEMENT WITH
EXERCISE THERAPIES
Tom Ainsworth1, Jyri Kermik1, Jonathan Woodham1 and Inam Haq2
Faculty of Arts and Architecture, University of Brighton, Brighton,
United Kingdom; 2Brighton and Sussex Medical School, Falmer,
United Kingdom
1
Background: Exercise therapies help to maintain functional ability in
patients with Rheumatoid Arthritis. Pinch grip, overall grip strength and
hand dexterity are the three hand functions most widely recognized as
having the greatest impact on functional ability and quality of life.
Devices are available to help maintain these functions, however,
many patients struggle to adhere to treatment recommendations. This
is reportedly due to fatigue, fear of injury, pain, and patients’ own
beliefs.
This study adopts an innovative design-led research approach
which aims to develop a new theory for improving patient engagement
with therapeutic exercise therapies.
Methods: Qualitative focus group study with two interviews with each
group.
Patients with RA aged 18-65 years were recruited by self-selection
in response to posters placed in patient waiting rooms and from
outpatient clinics.The focus group sessions were conducted at the
Royal Sussex County Hospital. Audio recordings were transcribed and
analysed for emerging themes using Content Analysis.
Results: 14 participants were recruited: 3 Male 11 Female, mean age
48.6 years (range 23-65), mean time since diagnosis 9.36 years (range
2- 22). Work Status: 4x unemployed (due to RA), 4x early retirement
(influenced by RA), 3x part-time (due to RA), 3x self employed.Existing
themes confirmed by this research include: pain, lack of time,
complexity of treatment regimen, patients’ own beliefs, fear of injury
and fatigue.
New themes identified:
1. Efficiency/Multi Functionality - interactive devices should support
the activities that people want, or need, to achieve anyway within
normal daily life, whilst also encouraging physical exercise.
2. More Able by Design - devices recommended to people with RA
should actively encourage physical health improvements wherever
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: Patient-reported outcomes (PROs) such as fatigue,
pain and sleep problems are common in RA. The REALISTIC (RA
EvALuation In Subjects receiving TNF Inhibitor Certolizumab pegol
[CZP]) 12-wk, Phase IIIb study evaluated CZP in a broad population of
patients (pts) with active RA, including those with prior TNF-inhibitor
use or receiving CZP monotherapy. The study presented here aimed to
determine the impact of CZP on fatigue, sleep problems and other
PROs in the REALISTIC trial.
Methods: 1,063 pts with active RA and an inadequate response to 1
DMARD were randomized 4:1 to CZP 400 mg (n ¼ 851) at Wks 0, 2 and
4 followed by 200 mg every 2 wks or placebo injection (control [ctrl]
n ¼ 212) every 2 wks added to current therapy. PROs included fatigue
(Fatigue Assessment Scale [FAS; 0-10 numeric rating scale]), sleep
quantity and quality (Sleep Problem Index II domain of the Medical
Outcomes Study sleep scale [MOS-SPI]), pain (0-100 mm visual
analogue scale [VAS]), and patient’s global assessment of disease
activity (PtGA, 0-100 mm VAS). The minimal clinically important
difference (MCID) is a clinically relevant change in a pt’s status. The
% of pts reporting MCIDs was determined: 1 for FAS, 6 for MOSSPI, and 10 mm for pain-VAS and PtGA. Correlations between PROs
and DAS28 were also assessed (Pearson correlations [rho], CZP group
only).
Results: BL characteristics were similar for CZP pts vs ctrl (FAS: 6.2
vs 6.4, MOS-SPI: 47.6 vs 48.1, pain VAS: 58.8 vs 62.3; PtGA: 59.2 vs
61.6). Statistically significant, meaningful improvements in fatigue and
sleep problems were reported with CZP vs ctrl from first measurement
to Wk 12 (Table 1). At Wk 12, more CZP pts had improvements MCID
in FAS (56.4% vs 46.2%, p < 0.01), MOS-SPI (49.7% vs 42.5%,
p ¼ 0.058), pain VAS (59.0% vs 42.0%, p < 0.001) and PtGA (59.5% vs
42.5%, p < 0.001). Correlations between PROs and DAS28 were
moderate (0.3 < rho < 0.6). Fatigue reductions poorly correlated with
improvements in haemoglobin levels (rho ¼ -0.10).
Conclusions: CZP treatment was associated with clinically meaningful reductions in fatigue and sleep problems, as well as improvements in pain and PtGA, in a diverse group of RA pts reflecting those in
clinical practice. The % of pts reporting MCIDs in PROs can easily
differentiate CZP vs standard treatment even in a short-term trial.
Correlation analyses showed that measurement of different PROs
consistently demonstrate the benefit of CZP in this population.
POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
possible. Many assistive devices, although helpful, do not
encourage therapeutic exercise and can lead to a reduction in
functional ability.
3. Reduce Feedback Loop - devices should provide realtime feedback to the user to assist with tracking performance and assist with
achieving pre-determined goals. This data could also be shared
with the wider healthcare team to help monitor and tailor ongoing
care.
4. Facilitate Social Connectedness - Social isolation, self-esteem and
information sharing, can all be improved through social interaction.
Social Networking websites and Apps could be tailored for
beneficial health purposes.
Conclusions: Evidence suggests that behaviour change caused by:
RA symptoms, patient attitudes and state of mind, and social
pressures, can lead to reduced functional ability in affected joints ‘learned non-use’. Treatment strategies should therefore target
behaviour change. This leads to Persuasive Design Theory defined
here as: design which seeks to change a person’s attitude or
behaviour for health benefit in concordance with their own wishes.
Disclosure statement: All authors have declared no conflicts of
interest.
Estefania Quesada-Masachs1, Ana Carolina Diaz1, Gabriela Avila1,
Isabel Acosta1, Xavier Sans1, Cayetano Alegre1 and Sara Marsal1
1
Rheumatology, Hospital Universitari Vall d’Hebron, Barcelona, Spain
Background: Targeting interleukin-6 receptor signal transduction by
tocilizumab (TCZ) has been shown to be an effective treatment for
patients with rheumatoid arthritis (RA). This study aimed to describe
safety and efficacy of tocilizumab (TCZ) in patients with rheumatoid
arthritis (RA) in routine clinical practice, based on prospectively
registered observational data from a third-level hospital.
Methods: Forty patients with RA who were started on TCZ at the
Rheumatology Unit between April 2009 and July 2011 were included.
Changes in tender joint count (TJC), swollen joint count (SJC),
erythrocyte sedimentation rate (ESR), haemoglobin (Hb), 28-joint
Disease Activity Score (DAS28), European League Against
Rheumatism (EULAR) response and remission rates with the 2011
American College of Rheumatology (ACR)/EULAR criteria after 4, 12,
24, 48, 72 and 96 weeks (W) were investigated. SPSS 17.0 program
was used for statistical analysis applying Student’s t-test for paired
samples. Adverse Events (AE) and withdrawals were also described.
Results: Thirty-five women and five men were included. Median age
was 52. Median disease duration was 11 (2-39) years. Rheumatoid
Factor was detected in 32 patients, anti-citrullinated protein antibody
in 30 and anti-nuclear antibodies were detected in 34 patients. Thirtyfour patients had previously received at least one biological treatment.
Decrease of TJC, SJC, ESR and DAS28 was statistically significant in
all the weeks. Increase of Hb was statistically significant until W48. The
analysis of the response data is summarized in Table 1. Regarding the
use frequency of concomitant treatments, the following information
compares the first and the last data recorded in each patient: diseasemodifying antirheumatic drugs in 60% to 48%; nonsteroidal antiinflammatory drugs in 80% to 35%; the average dose of corticosteroids (adjusted to prednisone dose) was initially 6.1 mg/day and finally
4.25 mg/day. Regarding safety, 31 patients (77.5%) had at least one
AE. The most frequent AEs were infections (22 episodes), dyslipidaemia (appeared in 16 patients) and haematology abnormalities
(detected in 14 patients). Three severe AEs were observed (community-acquired pneumonia, fever without source and acute toxic
hepatitis). There was no mortality in the group. Fifteen patients
(31%) withdrew from treatment for safety-related (25%) or non-safetyrelated (12.5%) reasons.
Conclusions: TCZ had achieved a good-or-moderate EULAR
response in 74% of patients with RA (80% TNFi failures) for 96
weeks in routine clinical practice. An early and maintained response
was observed. The most frequent AE were infections, dyslipidemia
and haematological abnormalities. The main causes of withdrawal
were AEs.
TABLE 1.
Baseline W4
DAS28 (average)
EULAR good-or-moderate
response rates (%)
Remission rates (%)
5.99
W12
W24
W48
W72
W96
4.37 3.33 2.96 2.83
2.36
2.06
74
86
90
80
100
100
3
29
27
25
30
25
Disclosure statement: All authors have declared no conflicts of
interest.
226. PREDICTING WHICH PATIENTS WITH EARLY
RHEUMATOID ARTHRITIS WILL CHANGE DMARD DURING
THE FIRST 2 YEARS: THE ERAN COHORT
Dan McWilliams1, Patrick D. Kiely2, Adam Young3 and
David A. Walsh1,4
1
Arthritis UK Pain Centre, University of Nottingham, Nottingham,
United Kingdom; 2Rheumatology, St Georges Healthcare NHS Trust,
London, United Kingdom; 3Rheumatology, West Hertfordshire
Hospitals NHS Trust, St Albans, United Kingdom; 4Rheumatology,
Sherwood Forest Hospitals NHS Foundation Trust, Sutton-inAshfield, United Kingdom
Background: Previous studies of the Early Rheumatoid Arthritis
Network (ERAN) cohort have shown that inflammation and disability
are major factors in predicting the initial DMARD regime [1]. This study
investigated possible clinical predictors for changing the first DMARD
within the first 2 years of treatment for early rheumatoid arthritis (RA).
Methods: ERAN is an inception cohort of newly diagnosed RA cases
given standard care in 22 hospitals in the UK and Eire, which
commenced in April 2002. Patients were included in this analysis if
they had enrolled in the cohort before July 2009. Those treated with
DMARD(s) were recorded and it was determined whether they had
changed therapy within 2 years. The reasons for change were
recorded, and risk factors for the commonest causes were investigated. Logistic regression analysis was performed to determine
associations between baseline factors and DMARD change before 2
years. Additional analyses used reduced logistic regression models
due to small numbers in subgroups. Significance was taken when
p < 0.05. Some non-significant variables are not shown.
Results: 1211 patients were enrolled in ERAN, and out of those eligible
for analysis 356 (29%) did not change their initial DMARD regime while
410 (34%) did change. Of those that changed, 51 (12%) were recorded
as Lack of Efficacy (LoE) and 147 (36%) as Adverse Drug Reaction
(ADR). In those included, the first DMARD treatment was recorded
as MTX monotherapy in 44%, SSZ monotherapy in 36% and
MTX þ HCQ þ SSZ combination therapy in 7% of the patients.
Significant baseline predictors of changing DMARD for any reason
are shown in table 1.
Analysis of the smaller subgroups for change due to ADR or LoE
incorporated fewer covariates due to small numbers. SSZ was
associated with change due to ADR (aOR 2.7, 95% CI 1.5 - 5.0).
Also, MTX (aOR 0.05, 95% CI 0.01 - 0.2) was negatively associated
with change due to LoE.
Conclusions: Patients treated in the first instance with MTX or triple
combination therapy for early RA appear more likely to remain on the
same treatment for the first 2 years. There are likely to be multiple
reasons for change in DMARD, and the clinical decision process is
complex. However, early initiation of definitive treatment including
MTX, in line with NICE guidance, could reduce morbidity and cost from
initial treatment failure.
TABLE 1 Predictors of DMARD change
Extra-articular disease
Disability
SSZ
MTX
MTX þ HCQ þ SSZ
aOR (95% CI)
p
1.8
1.4
1.1
0.6
0.3
0.050
0.005
0.789
0.076
0.014
(1.0
(1.1
(0.6
(0.3
(0.1
-
3.2)
1.9)
2.1)
1.1)
0.8)
Significant predictors and DMARD treatments are shown, along with adjusted
odds ratios (aOR) and 95% confidence intervals.
Disclosure statement: D.M. received a research grant from Pfizer.
D.W. received a research grant from Pfizer. All other authors have
declared no conflicts of interest.
Reference
1. Rachapalli SM, Williams R, Walsh DA, Young A, Kiely PD, Choy EH.
First-line DMARD choice in early rheumatoid arthritis—do prognostic factors play a role? Rheumatology 2010;49:1267–71.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
225. EFFICACY AND SAFETY OF TOCILIZUMAB IN
PATIENTS WITH RHEUMATOID ARTHRITIS IN CLINICAL
PRACTICE: TWO YEARS’ EXPERIENCE
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Wednesday 2 May 2012, 10.45 – 11.45
227. IMPROVED QUALITY OF LIFE AND PRODUCTIVITY
IN PATIENTS WITH MODERATE OR SEVERE RHEUMATOID
ARTHRITIS ACTIVELY SWITCHED TO TREATMENT WITH
INFLIXIMAB FROM ADALIMUMAB OR ETANERCEPT
THERAPY
Roy Fleischmann1, Rebecca Bolce2, Jianping Wang3, Mike Ingham2,
Ralph Dehoratius2 and Dennis Decktor2
1
Metroplex Clinical Research Center, University of Texas/
Southwestern Medical Center, Dallas, Texas, United States of
America; 2Medical Affairs, Janssen Services, LLC, Dallas, Texas,
United States of America; 3Bio Programming, Johnson & Johnson
Pharmaceutical Research and Development, LLC, Belle Mead,
New Jersey, United States of America
228. RISK FACTORS FOR MAJOR ADVERSE
CARDIOVASCULAR EVENTS IN RHEUMATOID ARTHRITIS
PATIENTS TREATED WITH TOCILIZUMAB
Vijay Rao1,2, Andrey Pavlov3, Micki Klearman1, Dave Musselman4,
Jon Giles5, Joan Bathon5, Naveed Sattar6 and Janet Lee4
1
Genentech, Genentech, South San Francisco, California, United
States of America; 2Division of Cardiology, UCSF, San Francisco,
California, United States of America; 3Everest, Everest, Toronto,
Ontario, Canada; 4Roche, Nutley, New Jersey, United States of
America; 5Division of Rheumatology, Columbia University, New York,
New York, United States of America; 6Rheumatology, University of
Glasgow, Glasgow, United Kingdom
Background: Associations of lipids, inflammation and RA disease
activity with risk of MACE were examined in TCZ-treated RA pts.
Methods: Post-hoc analyses of pooled data from phase 3 trials and
extensions were conducted in stepwise fashion. Demographic,
laboratory and disease measures were compared for pts with
(n ¼ 50) and without (n ¼ 3936) MACE (nonfatal myocardial infarction,
nonfatal stroke or CV death). Univariate Cox proportional hazard
modeling was used to evaluate potential risk factors for MACE at
baseline (BL) and post-BL (wk 24) with time to MACE as time variable;
multivariate Cox proportional hazard models were fit to obtain best
prediction of time to MACE. Statistically significant predictors were
considered as those with P < 0.05.
Results: For MACE during TCZ exposure, univariate modeling showed
BL age, history of cardiac disorders, statin use, TJC, SJC, DAS28, total
cholesterol (TC)/HDL ratio, ApoB and ApoB/ApoA1 ratio as predictive
(P < .05). Age, prior cardiac disorders, DAS28 and TC/HDL ratio were
robust predictors in multivariate model. Neither reduction in inflammation (CRP, ESR) nor lipid increases at 24 wks were statistically
significantly associated with future MACE on TCZ. Cox models using
single predictors and adjusting for age and BL values showed changes
in DAS28, AUC of DAS28, EULAR response, TJC and SJC at wk 24
were statistically significant predictors of future MACE (Table 1).
Greater reductions in DAS28, SJC and TJC from BL to wk 24 were
inversely associated with MACE (Table).
Conclusions: Univariate analysis showed traditional CV risk factors
and disease activity at BL were associated with MACE for pts on TCZ.
Only age, DAS28, TC/HDL, and history of cardiac disorders remained
statistically significantly associated with MACE on multivariate
analysis. Risk of MACE was broadly linked to elevated BL disease
activity and less robust therapeutic response at wk 24. There was no
association between lipid change and MACE risk. Mitigating CV risk in
RA pts may require a multifaceted approach including effective
disease activity control.
TABLE 1. Univariate Associations Between RA Parameters and Future MACE,
Adjusted for BL Age
Assessments
Wk 24
SJC (28)a,b
TJC (28)b
DAS28b
EULAR (Good vs. No Response)
AUC of DAS28 to wk 24, score-years
Change from BL to wk 24
Reduction in SJCb,c
Reduction in TJCb,c
Reduction in DAS28b,c
Age-adjusted Hazard
Ratio (95% CI)
P
1.092
1.054
1.351
0.295
1.714
1.136)
1.092)
1.633)
0.714)
2.886)
<0.0001
0.0034
0.0018
0.0067
0.0426
1.084 (1.034, 1.136)
1.043 (1.001, 1.086)
1.293 (1.043, 1.602)
0.0008
0.0439
0.0191
(1.051,
(1.018,
(1.118,
(0.122,
(1.018,
a
Interpretation of HR: After adjustment for age, 1 additional SJC at week 24 is
associated with 9% increased hazard for MACE; b Observed values; LOCF for
missing SJC or TJC at week 24; c Also adjusted for BL SJC, TJC or DAS28.
Disclosure statement: All authors have declared no conflicts of
interest.
229. A PROSPECTIVE SURVEY OF TOCILIZUMAB USE IN
SCOTLAND: IMPLICATIONS FOR DAILY PRACTICE
Derek Baxter1, John S. McLaren2, Margaret-Mary Gordon3 and
Kyaw Z. Thant4
1
Department of Rheumatology, Southern General Hospital, Glasgow,
United Kingdom; 2Fife Rheumatic Diseases Unit, Whyteman’s Brae
Hospital, Kirkcaldy, United Kingdom; 3Department of Rheumatology,
Gartnavel General Hospital, Glasgow, United Kingdom; 4Department
of Medicine, Wishaw General Hospital, Glasgow, United Kingdom
Background: Tocilizumab (TCZ) is a humanized interleukin-6 (IL-6)
receptor blocking agent for the treatment of severe rheumatoid
arthritis (RA). Approval was granted for use in Scotland in 2010 for
use in both methotrexate inadequate responders and TNF antagonist
failures. IL-6 plays a central orchestrating role in the inflammatory
response and contributes toward much of the adverse systemic
effects such as anaemia, osteoporosis and fatigue. The main adverse
effects reported in the pivotal trials, included increased hepatic
transaminases of up to 43%, neutropenia in up to a quarter and
adverse lipid profiles necessitating lipid lowering intervention. Our aim
was to survey both treatment efficacy in addition to recording the
frequency, magnitude and impact on treatment of adverse effects in a
‘real life’ setting in those treated with TCZ in Scotland.
Methods: All members of the Scottish Society for Rheumatology
were invited to participate. Data collection forms were sent to
Rheumatology units across Scotland in Spring 2010 and collated in
June 2011. Additional data was added through local databases where
available.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
Background: We evaluated the effect of infliximab (IFX) on quality of
life(Qol) and productivity in pts with moderate or severe RA actively
switched from adalimumab (ADA) or etanercept (ETN).
Methods: RESTART is a Ph4, multicentre, open-label, assessorblinded, active switch study of IFX in pts with active RA who received
MTX and had inadequate response (DAS28 score 3.6 & 6 swollen &
6 tender joints) to ADA/ETN. Pts were on stable dose of 7.5 mg/wk
of MTX for 4 wks prior to screening. Pts receiving ETN were switched
no less than 1wk and no more than 2wks after the last dose; pts
receiving ADA were switched no less than 2wks and no more than
4wks after the last dose. Pts received open-label 3 mg/kg IFX infusions
at wks0, 2&6. Pts who either achieved/maintained EULAR response at
wks14/22 remained on current IFX dose. IFX dose was increased by
2 mg/kg for pts who did not achieve/lost response. Evaluations
occurred at wk10 post induction and at wk26 following 2 additional
IFX doses at wk14&22. Pt functional status was assessed using the
HAQ-DI at wk10&26. Health Status was evaluated using EQ-5D & SF36. EQ-5D includes a descriptive 5-dimensional system for evaluating
current health status (each dimension has 3 response levels) and an
alternative method using a standard 20 cm VAS ‘‘feeling thermometer’’. Available algorithms allow scores on either dimension
responses or the VAS to be converted to a pt quality adjusted life
year (QALY) ‘‘utility’’ score. SF-36 requests pt health status over the
prior 4wks and reports on 8 dimensions and2 summary component
scales (Mental and Physical Health). Health economics data included
medical resource utilization, time lost from work/school&employability
at wk30.
Results: Data for 197/203pts enrolled were evaluable. 60.9% and
39.1% pts were previously treated with ETN or ADA, respectively.
Baseline (BL) demographics and efficacy were reported previously.
Mean HAQ score significantly improved from BL (1.334,CI:
1.252,1.415) at wk10 (-0.173,CI:-0.242, 0.105; p < 0.001) and wk26
(-0.223,CI:-0.303,-0.143; p < 0.001). % of pts who achieved significant
improvement (0.22 units) in HAQ score were 39.1% (CI:32.2%,
46.3%) at wk10 and 40.1% (CI:33.2%, 47.3%) at wk26. Change from
BL on all SF-36 domain scores significantly improved at wk 10&26.
Change in pt QALYs, taken from theEQ-5D also significantly improved
over BL (mean change of 0.106, CI: 0.073 to 0.140); p < 0.001).
Number of physician visits in the previous 8wks decreased at wk30
from BL. At wk30, no pts reported ER visits in the past 8wks. Pts
assessed their productivity as significantly improved at wk30 vs.
BL(1.42, CI:-1.86, 0.98; p < 0.001).
Conclusions: RA pts actively switched from ADA or ETN to IFX,
without a washout period, demonstrated a statistically significant &
clinically important improvement in QoL, health status and
productivity.
Disclosure statement: R.B. is an employee of Janssen. D.D. is an
employee of Janssen. R.D. is an employee of Janssen. R.F. is an
investigator for Janssen. M.I. is an employee of Janssen. J.W. is
an employee of Janssen.
POSTER VIEWING II
POSTER VIEWING II
Wednesday 2 May 2012, 10.45 – 11.45
Results: Data was available for 74 patients, median age 52 yrs
(18–90), median disease duration 11.5 yrs (1–27), 74% female and for
65/74 treatment indication was RA. Median number of previous
DMARDs was four (range 0-9) and biologic therapies three (range 0–5)
respectively. 43/74 (58%) were treated with concomitant methotrexate. Pre and post TCZ data (0 and 6 months) was available in 42
patients in whom median DAS28 fell from 5.96 to 3.69 (EULAR good
response 16/42 (38%) and moderate response 19/42 (45%)). Median
ESR reduction was 38 mm/hr to 5 mm/hr and CRP from 36 mg/l to
1.0 mg/l. Adverse events are shown in Table 1. After an overall median
of seven treatments, 17/74 of patients have discontinued TCZ of whom
7/74 (9%) discontinued owing to intolerance or side effect, 7/74 due to
inefficacy and 3/74 indefinitely suspended.
Conclusions: TCZ is a very effective therapy in those having failed
multiple biologic agents in this ‘real-world’ population. Adverse events,
most notably infection, are a frequent occurrence requiring treatment
suspension. Biochemical abnormalities are in keeping with published
trial data but through adjustments of concomitant DMARD therapy
or TCZ dose, rarely lead to prolonged treatment suspension or
discontinuation in daily practice. These results will help to inform local
monitoring policies as part of the administration of this therapy in order
to minimize interruption to therapy.
Adverse event
Number of patients
experiencing an
adverse event
Number of patients
requiring alteration
of TCZ schedule
Lipids
Liver Function Tests
Neutrophil count
Infection
Infusion reaction
23/74 (31%)
12/74 (16%)
15/74 (20%)
20/74 (27%)
6/74 (8%)
0/74 (0%)
2/74 (3%)
7/74 (9%)
12/74 (16%)
100% discontinued
Disclosure statement: D.B. received a research grant from Roche,
and speaker’s fees from Roche and Wyeth. M.G. received a travel
bursary from Roche. J.M. received funding support and a travel
bursary from Roche. K.T. received speaker’s fees from Roche.
230. USE OF INTRAMUSCULAR DEPOMEDRONE IN
INFLAMMATORY ARTHRITIS: DOES OBESITY INFLUENCE
RESPONSE TO INJECTION?
Emma L. Williams1, Susannah Earl2, Paula White3, Julie Williams3,
Sarah L. Westlake4 and Joanna Ledingham3
1
Bone & Joint Research Group, University of Southampton Medical
School, Southampton, United Kingdom; 2Rheumatology
Department, Royal Devon & Exeter NHS Foundation Trust, Wonford,
United Kingdom; 3Rheumatology Department, Queen Alexandra
Hospital, Portsmouth, United Kingdom; 4Rheumatology Department,
Poole Hospital NHS Foundation Trust, Poole, United Kingdom
Background: Intramuscular (i.m) steroid injections are widely used
both during treatment induction for inflammatory arthritis (IA) patients
& as treatment for acute symptom flares. Conventionally, these
injections are administered into the gluteal region, facilitating slow
release of steroid over a number of weeks. Patients usually respond
within 2 or 3 days but the degree and duration of response appear
highly variable. This study was designed to investigate whether
patients’ body habitus, indicated by body mass index (BMI) & waist
to hip ratio, influenced response to i.m steroid.
Methods: Patients were recruited from those attending Rheumatology
Clinic at a large district general hospital for management of their
inflammatory arthritis (IA). All patients offered an i.m injection
(120 mg depomedrone(DM)) as part of their standard treatment were
approached to participate in this study. Informed consent was
obtained prior to any study procedures. Ethical approval was obtained
from the local ethics committee. At baseline, each patient had their
height (cm), weight (kg), waist & hip circumference (cm) recorded.
Patients also completed a short questionnaire including visual
analogue scales (VAS) for pain, fatigue, well-being; Likert scales for
early morning stiffness (EMS), pain, general health & a medication
diary. Patients were given additional questionnaires to complete at
home & return by post at 2 and 6 weeks post injection.
Results: 180 patients were enrolled into the study. 104 patients
completed all aspects of the study; the remainder either withdrew or
had incomplete data. The majority of participants were female (65.4%),
as expected for a cohort with IA. Mean BMI was 29.8 (range 1864);mean waist:hip ratio was 0.9 (range 0.47-1.14). Over 69% of
patients reported reductions in pain & fatigue VAS & an improvement in
general well-being scores at 6weeks. Results at 2 weeks were very
similar, except more patients had reduced pain scores (70.2% vs
58.7%) and fewer had reduced EMS (39.4% vs 48.1%). Reduction in
pain VAS, fatigue VAS, reduced painkiller usage & improved well-being
at 6 weeks were significantly influenced by BMI (p 0.05). Only
improved well-being reached significance when considering waist:hip
ratio against the same outcome variables(p ¼ 0.049).
Conclusions: The above results suggest that patients’ BMI has a
significant influence on likelihood of response to i.m DM, most likely
due to injection into subcutaneous tissue rather than muscle, with
resultant impaired systemic steroid absorption. Interestingly, however,
waist:hip ratio did not reach significance against any of the outcome
variables except general well-being. Increasing patient numbers
further may well generate sufficient power to detect this difference.
In the interim, it seems prudent to consider giving i.m DM injections at
an alternative site such as the upper arm, in those patients with
significantly elevated BMI, in order to maximize response.
Disclosure statement: All authors have declared no conflicts of
interest.
SOFT TISSUE AND REGIONAL
MUSCULOSKELETAL DISEASE,
FIBROMYALGIA
231. SERUM 25-HYDROXY VITAMIN D LEVELS IN PATIENTS
WITH FIBROMYALGIA
Adnan K. Jan1, Azher I. Bhatti1, Catriona Stafford1, Martina Carolan1
and Sekharipuram A. Ramakrishnan1
1
Department of Rheumatology, Our Lady’s Hospital, Navan, Ireland
Background: There is an association between low levels of serum 25hydroxyvitamin D and non-specific musculoskeletal pain, including
fibromyalgia. Several studies reported a positive association, but
others did not show any link. We decided to study this in a cohort of
our patients with fibromyalgia.
Methods: The aim of this prospective study is to assess the serum 25hydroxy vitamin D levels in newly diagnosed fibromyalgia patients who
fulfilled the 1990 ACR (American College of Rheumatology) classification criteria for their diagnosis. A cohort of 40 newly diagnosed
consecutive fibromyalgia patients, attending our rheumatology outpatients has been included. Blood chemistry and Serum vitamin D
levels were taken at the time of diagnosis.
Results: 36 patients (90%) were females and 4 (10%) were males.
Mean age of patients was 46.8 years and median age was 49 years.
Serum Calcium and alkaline phosphatase levels were normal in all
patients. Deficiency of vitamin D (< 25 nmol/L) was observed in 11
patients (28%). 25 patients (62%) had vitamin D insufficiency (25–
80 nmol/L). In total 90% of patients (36/40) had vitamin D levels less
than 80 nmol/L (normal values for our laboratory).
Conclusions: There is a significant association between moderate to
severe vitamin D deficiency and fibromyalgia in our study. Its early
detection and replacement may have a therapeutic role in the
management of fibromyalgia symptoms. Large scale controlled
studies of Vitamin D levels in fibromyalgia and any therapeutic role
of replacing Vitamin D in such patients should be undertaken.
Disclosure statement: All authors have declared no conflicts of
interest.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Auckland on May 8, 2012
TABLE 1.
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