Presentation_FY 2014

Disease Modifying Drugs – DMDs – are drugs which modify the disease
course. They target inflammation and are designed to reduce the damage
caused by relapses. By doing this, the number and severity of relapses
decreases. Some of these drugs have been found to delay the long term
progression of MS and reduce the number of new lesions forming. Not
everyone with MS will benefit from DMDs in the same way. Guidance has
been issued by the Association of British Neurologists (ABN) setting out the
eligibility criteria for the prescribing of these drugs. See below, information
taken from their website:
ABN GUIDANCE FOR STARTING DISEASE MODIFYING
TREATMENT
All eligible patients will normally be ambulant (maximum EDSS 6.5) and
aged 18 or more years.
No treatments are licensed for use during pregnancy.
• Relapsing remitting multiple sclerosis. (ß-interferon or glatiramer
acetate). Patients with a diagnosis of active multiple sclerosis with
relapsing onset; active disease is defined by two clinically significant
relapses in the previous two years. Neurologists may, in certain other
circumstances where the evidence for efficacy is less secure, also
consider advising treatment after discussion with the patient concerning
the risks and benefits.
For example; (i) patients within 12 months of a clinically significant
clinically isolated syndrome when MRI evidence predicts a high likelihood
of recurrent episodes (i.e. development of multiple sclerosis).
(ii) patients with only a single major relapse in the preceding two years,
but combined with MRI evidence of continuing disease activity (i.e. meet
the revised McDonald criteria for MS)
(iii) Individuals aged less than 18 with relapsing remitting multiple
sclerosis.
• Aggressive multiple sclerosis. Patients with relapsing and
remitting multiple sclerosis that is considered to be rapidly evolving
and likely to prove severe in due course should be considered for
treatment with Natalizumab or Mitoxantrone by specialist
Choices
DISEASE MODIFYING DRUGS
(DMDs)
2
Disease Modifying Drugs (DMDs)
neurologists. Rapidly evolving and severe multiple
sclerosis is defined by two or more disabling relapses
in 1 year, with one or more gadolinium-enhancing
lesions on brain magnetic resonance imaging (MRI) or
a significant increase in T2 lesion load compared with
a previous MRI.
• Secondary progressive multiple sclerosis.
Treatment is not recommended in non-relapsing
secondary progressive multiple sclerosis and only in
relapsing secondary progressive multiple sclerosis
when relapses are the predominant cause of
increasing disability.
• Primary progressive multiple sclerosis.
No disease modifying treatment is indicated.
a first neurologic episode that lasts at least 24 hours,
and is caused by inflammation/demyelination in one
or more sites in the central nervous system (CNS). This
is sometimes diagnosed before a formal diagnosis of
MS can be made.
Those with CIS who show abnormalities on MRI scans
within one year, may be offered treatment with a
DMD provided it is agreed by the local health service
commissioners.
Four of the seven are licensed for CIS. These are:
interferon beta 1a (Avonex), interferon beta 1b
(Betaferon and Extavia), and glatiramer acetate
(Copaxone).
Source: www.theabn.org
There are currently seven DMDs available. These fall
into four categories:
• Interferon beta - there are two forms of
Interferons: Interferon beta-1a and Interferon beta-1b
(the differences between them are in the way they are
made)
• Glatiramer acetate (Copaxone)
• Fingolimod (Gilenya)
• Teriflunomide (Aubagio)
The criteria used to help decide who would benefit
from DMDs are:
Secondary progressive MS (interferon
beta only)
The following criteria must be met for starting on
treatment with interferon beta.
• You must be able to walk (at least 10 metres with
or without assistance)
• You must have experienced at least two disabling
relapses in the last two years
• You must have experienced minimal increase in
disability due to slow progression over the last two
years
Glatiramer acetate is not available for those with
secondary progressive MS (it has not been tested in
this type of MS).
Relapsing remitting MS
Before you can be considered for treatment with
interferon beta or glatiramer acetate:
• You must be diagnosed with MS
• You must be able to walk independently:
- with an EDSS of 6.5 or less for interferon beta,
meaning that you must be able to walk at least
10 metres with or without assistance
- with an EDSS of 5.5 or less for glatiramer acetate,
meaning that you must be able to walk at least
100m without assistance
• You must have experienced at least two clinically
significant relapses in the last 2 years
Clinically Isolated Syndrome (CIS)
Clinically Isolated Syndrome (CIS) is used to describe
The DMDs
Alemtuzumab (Campath/Lemtrada)
Alemtuzumab was originally licensed for the
treatment of leukaemia. It is an anti-CD52 monoclonal
antibody which kills T-cells, a type of lymphocyte
involved in the MS immune response. It basically
‘reboots’ the immune system. Once the t-cells are
killed (lymphocytes) the system then repopulates,
leading to a modified immune response that no longer
regards myelin and nerves as foreign.
The drug received NICE appraisal as an NHS treatment
in May 2014. The Scottish Medicines Consortium (SMC)
is due to publish a decision on the use of the drug in
July.
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Disease Modifying Drugs (DMDs)
Fingolimod (Gilenya)
Fingolimod (Gilenya) is an oral drug licensed for people
with rapidly evolving severe relapsing remitting
MS or as a treatment for those who have not seen
sufficient improvement from front-line treatments
such as the DMDs listed above. Fingolimod is an
immunomodulating drug, which attaches to the
surface of certain white blood cells, a number of
which will be retained within the body’s immune
system. Fewer lymphocytes are then able get into the
bloodstream and reach the CNS. The immune attack
on the cells of the brain and spinal cord is potentially
reduced.
Possible side-effects include headache, upper
respiratory tract infection, shortness of breath,
diarrhoea and nausea. Fingolimod can cause a
decrease in heart rate so the first dose will be
monitored in hospital for six hours. It should be stored
below 30c and be protected from moisture.
Interferon beta-1a
Interferons are proteins, produced naturally by the
body, helping us to fight infection. There are currently
two Interferon beta-1a DMDs available – Avonex and
Rebif.
Avonex blocks the action of one type of protein
called gamma interferon. It reduces the autoimmune
reaction that causes inflammation and destruction
of myelin. It has been shown to reduce the rate of
relapse by about one-third in people with relapsing
remitting MS. It also reduces the severity of relapses
that occur. It must be injected into the muscle once a
week and should be stored in the fridge between 2c
and 8c.
Rebif is like Avonex in that it also works to block the
action of the gamma interferon protein. However,
Rebif has to be injected under the skin 3 times per
week and should also be stored in the fridge between
2c and 8c. It has the same success rate in reducing
relapse rates and their severity.
The most common side-effect experienced with
both of these treatments is flu-like symptoms after
injecting and the injection site may have redness or
swelling, or sometimes itching. They can also cause
changes in menstruation, blood abnormalities and
mood swings; however, these symptoms are less
common. Most people find that these side effects
disappear after 3 months. If the side-effects persist, a
conversation with the MS nurse or neurologist would
be recommended.
Glatiramer acetate
Glatiramer acetate or otherwise known as Copaxone.
This drug works differently to Betaferon in that it is
a synthetic combination of four amino acids which
resemble the myelin protein. It is thought to work by
preventing the production of immune cells that attack
myelin. The rate of relapse in people taking Copaxone
is generally reduced by a third and is prescribed for
those with relapsing-remitting MS and also Clinically
Isolated Syndrome. Copaxone needs to be injected
under the skin every day. Common side-effects are
injection-site reactions and lipotrophy (indentations
under the skin). This DMD can also cause chest
tightness, breathlessness, anxiety, flushing and
palpitations after injection. However, these symptoms
are less common and they typically pass within a few
minutes.
Interferon beta-1b
There are currently two Interferon beta-1b DMDs
available – Betaferon and Extavia. They are both
injected under the skin on alternate days and both
reduce the rate of relapse by about one-third in people
with relapsing-remitting MS. The most common sideeffects experienced with both of these treatments
are flu-like symptoms after injecting and injection
site reactions. They can also cause changes in
menstruation, blood abnormalities and mood swings;
however, again these symptoms are less common.
Teriflunomide (Aubagio)
Teriflunomide is an oral compound that inhibits the
function of specific immune cells that have been
implicated in MS. It can inhibit a key enzyme required
by white blood cells (lymphocytes) – which in turn
reduces the T and B immune cells that are active in
MS, from multiplying. As well as this, it has shown to
have other anti-inflammatory and immunomodulating
actions. Teriflunomide received NICE approval as an
NHS treatment in January 2014.
Tysabri
A monoclonal antibody called Tysabri is also available
as a treatment for MS. However, it works differently
MS-UK Unsworth House, Hythe Quay, Colchester, Essex, CO2 8JF
Tel: 01206 226500 Email: [email protected] www.ms-uk.org
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Disease Modifying Drugs (DMDs)
to DMDs and is not technically classed as a ‘Disease
Modifying Drug’. It works by preventing immune
cells leaving the blood stream and entering areas of
inflammation. Tysabri has to be given by intravenous
infusion every 4 weeks at either an infusion centre or
a hospital.
For more information, please see our choices leaflet
‘Tysabri’.
Coping with side effects
The side effects of these drugs are generally not
severe and there are various ways to manage them.
If you suffer from flu-like symptoms after injecting,
try changing the time of day you take your injection;
possibly to just before bedtime so you can sleep
through the side-effects. Alternatively, it is
recommended to take paracetamol or ibuprofen two
hours before the injection to ease the side-effects.
If you suffer from injection-site reactions, you could
try using Emla cream which numbs the area prior to
the injection. Always rotate the injection site – avoid
injecting the same area each time. It may also help
to ensure the drug is at room temperature and also
warming the skin before injecting may help make your
injection more comfortable.
If your side-effects do become severe or you feel
unable to cope with them, contact your MS nurse
or neurologist who will be able to advise you
further. Contact our advice and information line on
0800 783 0518 to find your nearest MS nurse.
Lifestyle
Once diagnosed with MS, your neurologist will talk
to you about any medication you may require and
be eligible for. They will discuss with you all your
possible options. One thing to consider when looking
at these medications is your lifestyle and how the
administration of these drugs will fit into your day-today living.
When choosing your medication, one main
consideration is deciding how often you inject. If
you choose to inject once a week (e.g Avonex), which
day do you do it (bearing in mind that you may have
side-effects to deal with after)? For example: if you
work all week and inject on a Friday, you may ‘lose’
your weekend because of possible flu-like symptoms
that may wipe you out. Alternatively, you may prefer
to inject every day (e.g.Copaxone) and avoid flulike symptoms but possibly experience injection
site reactions and skin indentations. It is however,
important to remember that not everyone experiences
these side-effects.
Another consideration is how are you with needles?
Some people have a real phobia about them. Would
you prefer someone else to administer the medication
for you? If so, who would that be and are they available
to help you? Many of the drugs mentioned can be
injected using an ‘auto injector’. The auto-injector is
a handheld device that hides the needle. Using an
auto-injector means you do not actually have to ‘inject’
yourself, you just hold the button on the auto-injector
and it does it all for you.
Whichever you choose, there is an element of trial and
error involved so it is advisable to look at your lifestyle
first and pick the best of the choices that is right for
you. Openly discuss all the options with your MS nurse
and/or neurologist to come to a joint decision as to
what is the best course of treatment for you.
DRUGS IN DEVELOPMENT
All drugs need to be licensed and go through
regulatory procedures before they are made available.
Many drugs are currently being developed to treat
multiple sclerosis. The list below contains drugs that
are either currently in trials or have completed their
trials but are not yet licensed. Some have been put
forward for European licensing.
Tecfidera (BG-12)
BG-12 may have an anti-inflammatory effect on
the immune system. The FDA approved Tecfidera
capsules on 27 March 2013 to treat adults with
relapsing-remitting forms of MS. License was granted
for treatment of adults with RRMS. In February
2014 Tecfidera was approved by the EMA (European
Medicines Agency). It is now undergoing a NICE
appraisal with a decision expected in 2014.
MS-UK Unsworth House, Hythe Quay, Colchester, Essex, CO2 8JF
Tel: 01206 226500 Email: [email protected] www.ms-uk.org
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Disease Modifying Drugs (DMDs)
Laquinimod
Laquinimod affects the level of certain cytokines
(substances released by immune cells) and reduces
the passage of immune cells into the brain and spinal
cord. Studies have also suggested that this drug
may have a protective effect on the nervous system
and anti-inflammatory actions. The manufacturer
submitted laquinimod for licensing in Europe. A
decision by the European Medicines Agency (EMA) is
expected in 2013. A decision on the NICE appraisal is
expected in February 2014.
Ocrelizumab
Early results from trials indicate that ocrelizumab
is twice as effective as current DMD’s for relapsing
remitting MS. Trials for relapsing remitting MS are due
to finish in 2015 and trials for primary progressive MS
are due to finish in 2017. The side effects seen in trials
were comparable in all treatment groups and serious
side effects were rare. It works by targeting the CD20
marker on the surface of B cells. These are thought
to influence how the immune response causes the
immune system to attack myelin.
was found to have significantly less reduction in
brain volume, significantly slower change in EDSS,
and significantly improved scores on the MSIS-29
(a measure of the extent to which MS affects daily
life). The trial is in phase II and this small study is not
sufficient evidence for the routine use of simvastatin
in secondary progressive MS. The beneficial results
will need to be confirmed by further studies with more
participants.
Siponimod
Siponimod is in phase 3 trial for secondary progressive
MS and is a tablet taken once daily. It belongs to
the same class of drugs as fingolimod (gilenya). In
previous trials for relapsing remitting MS the drug
reduced relapse rate compared to placebo. The drug is
designed to work on certain types of white blood cells
(lymphocytes). These are cells that are involved in the
attack on myelin. The drug causes the lymphocytes to
be retained in the lymph glands, resulting in a reduced
immune attack on nerve cells in the brain and spinal
cord.
Masitinib
Masitinib is currently in phase 2 trials for secondary
progressive MS and phase 3 trials for primary
progressive MS. The estimated completion for these
trials is late 2014. It is an oral tablet that is to be taken
twice daily. It is designed to target mast cells, which
are cells involved in allergic reactions. In doing this it
helps to block some of the processes involved in the
inflammatory and immune responses.
Daclizumab
Daclizumab is currently in phase 3 trials for relapsing
remitting MS. The study is called DECIDE which is
comparing the drug with interferon beta 1a (Avonex)
in patients with RRMS. It is due to finish in March
2014. Another study called SELECT will look at the
long-term safety and effectiveness of the drug. The
estimated completion date is May 2015. Daclizumab
is a monoclonal antibody, it blocks the activity
of the chemical messenger interleukin 2, in the
immune system. It also helps prevent the growth of
lymphocytes.
Simvastatin
A small-scale study (140) of people with secondary
progressive MS has been in progress for two years and
has shown that the group taking 80mg of simvastatin
Updated May 2014
MS-UK Unsworth House, Hythe Quay, Colchester, Essex, CO2 8JF
Tel: 01206 226500 Email: [email protected] www.ms-uk.org
Charity No. 1033731
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