Fourth edition August 2009

06
Disease modifying drugs

MS Essentials
For people living with MS

This publication is available in large print (22 point) Call 020 8438 0799 or email infoteam@mssociety.org.uk
Disease modifying drugs are not a cure for multiple sclerosis (MS), but they can reduce the number and severity of relapses. One of the drugs licensed for MS, natalizumab (brand name Tysabri), has also been shown to slow the progression of disability over two years.1, 2 It is not yet known whether any of these drugs will slow down the rate of disability in the long term. If you are experiencing relapses with your MS, disease modifying drugs might be a suitable treatment.3, 4 Unfortunately, research to date has shown that these drugs are of no benet for people with primary progressive MS.5 Several different disease modifying drugs have been licensed for MS and are available on the NHS for those who meet the criteria:

natalizumab (brand name Tysabri) beta interferon 1a (two brands available Avonex and Rebif) beta interferon 1b (two brands available Betaferon and Extavia) glatiramer acetate (Copaxone) This booklet might help you decide if disease modifying drugs are a suitable option for you. We look at the differences between these drugs, who is eligible on the NHS, and the practicalities of taking them. You may need to choose between several drugs and this booklet might help with that decision. We also look briey at less commonly used disease modifying drugs and emerging treatments, some of which are expected to apply for licensing in 2009.

Contents
02 What are the disease modifying drugs? 03 Who is eligible for these drugs on the NHS? 06 Who prescribes these drugs? 07 Can I pay privately for these drugs? 07 Frequently asked questions natalizumab 08 Side effects natalizumab 10 Frequently asked questions beta interferon and glatiramer acetate 16 Side effects beta interferon and glatiramer acetate 18 Other disease modifying drugs 20 Further information

What are the disease modifying drugs?

This booklet concentrates on the licensed MS disease modifying drugs that are available on the NHS: natalizumab, beta interferon 1a, beta interferon 1b and glatiramer acetate.

Natalizumab (Tysabri)
How does it work? Natalizumab (pronounced nat-al-iz-yoo-mab) is an antibody, just like those found naturally in the immune system (where antibodies help ght infection). By attaching itself to receptors on the outside of certain immune cells, natalizumab prevents these cells from leaving the blood stream and entering the brain and spinal cord where, in MS, they can cause inammation and damage. Whats the evidence? A two-year study showed that, on average, people taking natalizumab had a 67 per cent reduction in the number of relapses (compared to what would be expected if no treatment was taken). Natalizumab also slowed the accumulation of disability over two years. Only 17 per cent of people taking the drug had worse disability, compared with 29 per cent of people taking a placebo (dummy treatment).1, 2 We do not yet know if natalizumab can deliver long-term benets. How is it taken? Natalizumab is given by a health care professional as a monthly infusion into a vein, lasting about an hour. This usually happens at the neurology unit of a hospital.

Beta interferon and glatiramer acetate (Avonex, Rebif, Betaferon, Extavia and Copaxone)
How do they work? Interferons are proteins produced naturally in the human body. There are different types of interferon, including alpha, beta and gamma. In the immune system, they help ght viral infections. Its thought that beta interferon can reduce (and might prevent) inammation which can damage nerve bres in MS. The different beta interferon drugs are named 1a and 1b because of differences in how they are manufactured. The branded drugs Avonex, Rebif, Betaferon and Extavia are all beta interferons. Glatiramer acetate is a drug designed to mimic the main proteins in the fatty coating around nerve bres (called myelin). Its thought that the drug works by connecting to cells to stop them attacking the myelin and causing MS symptoms. The branded drug Copaxone is glatiramer acetate.

Disease modifying drugs MS Society 08/09

Whats the evidence? In drawing up guidelines for the use of beta interferon and glatiramer acetate, the Association of British Neurologists (ABN) looked at several clinical trials. They considered that the different drugs are equally effective for those eligible, with around a 33 per cent reduction in the number of relapses experienced over two years (compared to what would be expected if no treatment was taken). They also noted that relapses could be less severe for those taking the drugs.3 There is no clear research evidence for long-term benets. How are they taken? These beta interferon and glatiramer acetate drugs are all selfinjected, between one and seven times a week, depending on which drug is used. There is more about injecting and the differences between the drugs in later sections of this booklet.

Who is eligible for these drugs on the NHS?

The drugs are licensed for certain people who experience relapses. Depending on how your MS affects you, there may be a choice between several drugs.

Who decides if I am eligible?

The National Institute for Health and Clinical Excellence (NICE) assesses new drug treatments and recommends whether or not they should be made available on the NHS in England, Wales and Northern Ireland. The Scottish Medicines Consortium (SMC) carries out a similar role north of the border. Final decisions to prescribe rest with individual neurologists. As with other treatments, you can ask for a second opinion if you are not happy with the advice a doctor gives you.

Natalizumab
In 2007, NICE published its guidance for natalizumab.4 The guidance recommends NHS prescribing of natalizumab for adults with rapidly evolving, severe, relapsing remitting MS. Broadly speaking, this means people who have two or more disabling relapses in a year and have signs of new MS inammation on a recent MRI scan (compared with a previous scan). If your MS is less active than this, you may be eligible for one of the other licensed disease modifying drugs. The full recommended criteria are available from NICE (www.nice.org.uk or 0845 003 7780).
Disease modifying drugs MS Society 08/09

If you and your neurologist feel you meet the criteria, it should be available to you on the NHS. At the moment, however, this is not always the case. If you feel you meet the criteria, but have difculty accessing natalizumab, the campaigns team would like to hear from you, and they may have further information which can help your case. Call 020 8438 0700 or email campaigns@mssociety.org.uk

Beta interferon and glatiramer acetate

In 2001, NICE decided that beta interferon and glatiramer acetate did not provide enough benet for them to be available on the NHS. However, challenges to this decision led to an agreement between the Government and the drug companies to make the drugs available through what is known as the Risk Sharing Scheme.

Why is it called the Risk Sharing Scheme? The risk in the title refers to a shared nancial risk if the drugs do not prove to be as effective as was promised, then the drug companies could be required to reduce the price of the drugs to the NHS. Around 5,500 people taking these drugs have been recruited for monitoring, to assess their effects in the long term.

The Association of British Neurologists (ABN) has issued guidelines on the use of beta interferon and glatiramer acetate. These guidelines are used in the Risk Sharing Scheme. They set out criteria for starting and stopping treatment and help neurologists to identify people who may benet from the drugs.3 Anyone who meets the criteria is entitled to the drugs on the NHS, wherever they live in the UK. You can get the complete ABN guidelines online at www.theabn.org or ask the MS Society Information Team to send you a copy by post. Here is a summary of the ABN criteria that would make you eligible for starting treatment on the NHS: If you have relapsing remitting MS
Disease modifying drugs MS Society 08/09

The following criteria need to be met before you can be considered for treatment with beta interferon or glatiramer acetate:

you must be able to walk at least 10 metres, with or without assistance (or 100 metres without assistance for Copaxone) you must have experienced at least two clinically signicant relapses in the last two years

If you have secondary progressive MS The following criteria need to be met before you can be considered for treatment with beta interferon (glatiramer acetate is not available for people with secondary progressive MS):

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 only minimal increase in disability because of slow progression (if you have had increased disability, it needs to have been mainly caused by relapses)

What counts as a relapse? A clinically signicant relapse can be dened as a period when a person experiences an acute worsening of symptoms that lasts for at least 24 hours and is followed by an improvement for at least one month. Relapses are usually much longer than 24 hours and a common duration is between one and four weeks. Sometimes MS deteriorates temporarily because of having a fever for example, with the u or a bladder infection. These episodes are not relapses. A disabling relapse is not dened in the ABN guidelines, and is judged by individual neurologists in each case.

What if I have been diagnosed with a clinically isolated syndrome?

Some people in the UK are receiving beta interferon on the NHS after a clinically isolated syndrome. In each case, the local health services commissioners have agreed to fund the treatment for that person. A clinically isolated syndrome is a set of symptoms which, like MS, may well be due to damaged myelin around nerve bres, but where there have been no other attacks. Optic neuritis is a common example. Some people with a clinically isolated syndrome go on to have further attacks and, if test results support it, are diagnosed with MS. Some people never develop MS and the clinically isolated syndrome will remain an isolated incident. There has been a great deal of debate about the long-term value of taking beta interferon after a clinically isolated syndrome. The 2001 ABN guidelines do not recommend it. NICE are looking into this subject in 2009. Any changes in recommendations will be reported on the MS Society website (or contact the Information Team).

Disease modifying drugs MS Society 08/09

Children and adolescents

Although much of the information and guidance for doctors on disease modifying drugs relates to adults, beta interferon and glatiramer acetate can be prescribed to children and adolescents by a neurologist. Since the ABNs 2001 guidelines, studies have shown that beta interferon and glatiramer acetate are safe to use to treat MS in those under 18 years old.6, 7, 8 Children are being prescribed these drugs in the UK and, more widely, in the USA and Canada. Natalizumab is not normally prescribed for children and there have not been studies to show its safety for under-18s. The MS Society booklet Childhood MS a guide for parents has more about managing MS in children (see Further information).

Who prescribes these drugs?

Natalizumab
Natalizumab can be prescribed on the NHS by any neurologist, just like any other prescription drug with the same considerations around suitability, potential benets and possible side effects. A neurologist would be guided in their decision to prescribe by the NICE guideline for the drug. Because of rare but potentially very serious side effects, anyone taking natalizumab needs to be carefully monitored, with regular check-ups.

Beta interferon and glatiramer acetate

When the Risk Sharing Scheme was rst launched, these disease modifying drugs were only prescribed on the NHS at certain prescribing centres. There were 70 of these around the country. Now, however, far more neurology departments are prescribing the drugs and there is a prescribing centre in most large towns and cities. If your neurologist is not based at a centre which prescribes these drugs, they might refer you to your nearest centre for this. You can still choose to see your existing neurologist for other matters. This is something to discuss with them when they make the referral. Your neurologist and the neurologist at the prescribing centre (if you are referred), will use the ABN criteria as a guide for the assessment. While taking a disease modifying drug, you will have regular review appointments with your MS nurse and an annual assessment by a neurologist at the prescribing centre.

Disease modifying drugs MS Society 08/09

Can I pay privately for these drugs?

Like any other licensed drug, disease modifying drugs are available on private prescription. If you are considering this, there are certain things worth bearing in mind:

A neurologist will need to prescribe the drug. Going private cannot guarantee a drug will be suitable or effective for you. A neurologist is likely to consider the guidance and recommendations from the Association of British Neurologists and NICE when considering whether to prescribe. All ve licensed drugs cost several thousand pounds per year. These are all drugs which you might take for many years. Ongoing consultations and monitoring with the prescribing neurologist may also need to be on a private basis.

Frequently asked questions natalizumab

This section tries to answer frequently asked questions from people considering disease modifying treatment with natalizumab. Possible side effects are covered in the following section.

How long will I be prescribed the drug?

There are no formal guidelines for stopping treatment with natalizumab. You could expect to take it for as long as you and your neurologist agree it seems to be working. If the side effects become a problem, or blood tests show early signs of health problems, these would be reasons to stop. Occasionally, the immune system begins to act against natalizumab and stop it working. If this occurs at all, it is normally in the rst six months of treatment, when it would show up with a blood test. This can sometimes be a reason to stop taking natalizumab.

How will taking natalizumab affect any other treatments?

Because of the way it works, natalizumab is not suitable for people with weakened immune systems, so it cannot be combined with treatments which alter the way the immune system works, such as the other disease modifying drugs. People taking natalizumab can still receive short courses of steroids to treat relapses.
Disease modifying drugs MS Society 08/09

Does natalizumab affect pregnancy or breast feeding?

As with the other licensed disease modifying drugs, it is not known if natalizumab presents a risk to the foetus and babies. If you are trying to conceive or are already pregnant, it is important to discuss all your medications with your doctor. Women are advised to stop taking natalizumab if they are trying to conceive, are pregnant or breastfeeding. Speak to your neurologist for further advice on this.

Is natalizumab vegan-friendly or vegetarian-friendly?

Natalizumab is made by combining DNA from mouse and human cells, to create an antibody similar to those in the human immune system. As with other licensed drugs, natalizumab has been tested in animals.

Side effects natalizumab

Most people taking natalizumab tolerate it well, but there can be side effects including a very rare, but potentially fatal infection called PML (see opposite). To minimise this risk, everyone taking natalizumab is monitored closely.

Ongoing monitoring if you take natalizumab

Each month, when you visit the clinic for your infusion, the doctor or nurse will ask if you have any lasting medical problems which are getting worse, such as changes to eyesight, your memory or thinking, or balance. They will also ask specic questions about any reactions you might have noticed after the last infusion of natalizumab, or any fever or infection. One reason they ask these questions is to pick up any early signs of PML (see opposite).

During or shortly after the infusion

During the infusion of natalizumab, and up to an hour afterwards, some people shiver, feel sick or dizzy. These effects are usually mild and normally pass before the end of the infusion. They are not usually a reason for having to stop the treatment. Around one in 25 people who take natalizumab have a more serious allergic reaction to taking it, either during the infusion or in the hour following. These kind of hypersensitivity reactions are more serious than those mentioned above. An allergic reaction can include an itchy rash, swelling of the face, lips or tongue and difculty breathing.

Disease modifying drugs MS Society 08/09

Other signs of an allergic reaction might be picked up by health care professionals, such as an increased body temperature, decreased blood pressure and a faster pulse. The health care team would give medical attention if this reaction occurs, to manage the symptoms. Treatment with natalizumab has to be stopped for anyone who has an allergic reaction to it.

Common side effects

Common side effects include joint pain, fever, tiredness, a runny or blocked nose, sore throat, feeling or being sick, headache or dizziness. Fewer than ten per cent of people taking natalizumab experience these side effects, but these milder side effects are far more common than, for example, liver problems or PML.

PML (progressive multifocal leukoencephalopathy)

Because of the way that natalizumab works, it can leave the immune system more open to infections. PML is a viral brain infection. It can cause severe neurological symptoms, which may at rst be mistaken for MS relapses. But the symptoms rapidly worsen and may lead to death. Several people treated with natalizumab have died because of PML. One large study suggests the chance of developing PML for someone using natalizumab for 18 months is around one in 1,000. This study looked at over 3,400 people taking natalizumab, but they did not all have MS. The long-term risk is not yet known.9 Any hospital prescribing natalizumab must ensure that everyone professionals and patients is aware of the risks, the early signs of PML to look out for and what to do if they notice these signs.

Liver problems
Serious liver problems for people taking natalizumab are also very rare and ought to be picked up in routine blood tests. Early signs of liver problems include the skin or whites of the eyes turning slightly yellow, and urine turning unusually dark.

Long-term side effects

It is too soon to know about possible long-term side effects from natalizumab, but people taking the drug are being monitored, which should give a better picture for the future.

Disease modifying drugs MS Society 08/09

Frequently asked questions beta interferon and glatiramer acetate

This section tries to answer some of the frequently asked questions from people considering disease modifying treatment with beta interferon or glatiramer acetate (Avonex, Rebif, Betaferon, Extavia or Copaxone). Many people eligible for one of these drugs will have a choice of which to take. As with any treatment, its a case of weighing up the pros and cons. Possible side effects are covered in the next section.

Which drug will benet me most?

Unfortunately, it is impossible to say which drug is more effective for any particular person. Results from clinical trials can only tell us the average benets for people. As with any average, some people will benet more and some will benet less than the average. Clinical trials have not clearly shown that any of the four drugs are more effective than the others. Out of four clinical trials comparing one with another, two trials suggested there was no signicant difference between beta interferon and glatiramer acetate. The other two trials have suggested beta interferons were slightly more effective when injected every other day or three times a week compared to beta interferons injected only once a week. However, this slight difference might not be carried on beyond two years, when neutralising antibodies could possibly come into play (see below).10, 11, 12, 13

What are neutralising antibodies? Sometimes, the bodys immune system begins to react against beta interferon, by producing antibodies which might prevent the drug from being effective.14 Experts disagree about how much these antibodies can affect the way the drugs work. In some cases, levels of antibodies go down over time. Sustained, high levels of neutralising antibodies can be a factor in choosing to stop treatment.3

How do I choose?
Disease modifying drugs MS Society 08/09

To choose between the beta interferons and glatiramer acetate, you will need to discuss the issues with your neurologist and, if you have one, your MS nurse. They will be able to talk about experiences others have had, and about medical considerations over which drug is suitable. But your choice will also depend on your own preference about, for example, how often you want to inject and what will suit you best. The information in the table on page 12 and in the other frequently asked questions might help you consider the options.

10

The table gives a quick overview of the differences in frequency, preparation and storage of the drugs available in the Risk Sharing Scheme. If you have access to the internet, you might also nd the site www.msdecisions.org.uk useful. Produced by the University College London Hospital NHS Trust, with Department of Health funding, the site includes an online decision tool.

What am I committing to?

Taking any of these disease modifying drugs involves a long-term commitment. They are intended to reduce the number and severity of relapses over several years, so they need to be taken regularly for some time. As long as the drug seems to be having a positive effect (for example, if your relapses are less severe or less frequent than before) it should continue to be prescribed. However, there might be circumstances in which you decide, together with your neurologist, to stop taking a disease modifying drug, such as:

if you or your health care team notice signs of a serious side effect or adverse reaction if you nd the side effects intolerable if you are planning to get pregnant if you develop an increased number and severity of relapses if you do not see a reduction in the number of relapses compared to the one to two years before you started taking it if you develop neutralising antibodies (see opposite) if you develop secondary progressive MS and can no longer walk if a more suitable treatment becomes available Treatment on the NHS should not be stopped for nancial reasons. If your MS becomes more active and you become eligible for natalizumab, this might be a reason to discuss changing treatments with your neurologist. Natalizumab is not licensed for combination with any of the other disease modifying drugs, so you would stop taking one drug before beginning the other.

11

Disease modifying drugs MS Society 08/09

Comparing the drugs Drug name How often is it injected?

Once a week

Where is it injected?
Into the muscle

Is the drug pre-mixed, ready to inject?

It is available in two versions: one is pre-mixed and ready to inject; the other needs to be mixed each time.

How should it be stored?

Avonex
(beta interferon 1a)

The pre-mixed version generally needs to be kept in the fridge (2 to 8C), but can be kept at room temperature for up to a week before use. The unmixed version can be kept at room temperature for up to two years.

Rebif
(beta interferon 1a)

Three times a week

Under the skin

Yes, it is pre-mixed

In the fridge (2 to 8C). The makers provide cool bags for travel.

Betaferon
(beta interferon 1b)

Alternate days

Under the skin

No, it needs to be mixed each time

At room temperature, for up to two years.

Extavia
(beta interferon 1b)

Alternate days

Under the skin

No, it needs to be mixed each time

At room temperature, for up to two years.

Copaxone
(glatiramer acetate)

Every day

Under the skin

Yes, it is pre-mixed

Generally needs to be stored in the fridge (2 to 8C), but can be stored at room temperature (15 to 25C) for up to a month before use.

Disease modifying drugs MS Society 08/09

12

13

Disease modifying drugs MS Society 08/09

Can I switch drugs?

Yes, if you need to, you can switch to another of the drugs that you are eligible for. You would need to discuss any planned change with the prescribing neurologist. Peoples reactions to drugs vary and if, for example, you get continuing side effects which prove intolerable, you might want to change drugs. Note that if you switch from a beta interferon because of neutralising antibodies (see page 10), it only makes sense to switch to glatiramer acetate the antibodies will neutralise other forms of interferon as well.

Do I have to inject myself?

These drugs do need to be injected, but most people, even many who were afraid of needles, nd that they soon get used to it. None of the drugs are injected into a vein. Instead, they are injected just under the skin or into the muscle. The drugs are available with auto-inject a system which means you dont need to see the needle going in, and where the action of injecting comes down to the click of the pen holding the syringe. A new device has recently been launched for one of the beta interferons, Rebif. Known as RebiSmart, this new injecting device has pre-lled syringe cartridges which only need loading once a week. The device allows for changing needles and injecting without having to see the needle itself, and also keeps a record of when the injections happen. If you are prescribed beta interferon or glatiramer acetate, a nurse will go through good injection technique with you. Most people nd they are able to do the injections themselves, which gives them independence over when and where to do it, but it is possible for a family member or friend to be given this training so they can do it for you. It is also sometimes possible for injections to be given by a practice nurse at a local clinic.

How do I store the drugs and syringes?

Different drugs have different storage requirements, as shown in the table on page 12. Most need to be kept in the fridge, and you would also need to have a safe space to store syringes and discarded needles. The drug company will supply a box for these discarded sharps. An MS nurse can help with storage ideas and how to approach family or friends who you might want to explain things to.

Disease modifying drugs MS Society 08/09

Do these drugs affect pregnancy or breast feeding?

It is not known whether beta interferon or glatiramer acetate present a risk to a baby or foetus. If you are trying to conceive

14

or are already pregnant, it is important to discuss all your medications with your doctor. Women are advised to stop taking a disease modifying drug if they are trying to conceive, are pregnant or breastfeeding. You should discuss all these matters with your doctor.

What about travelling with the drugs?

Taking these drugs should not prevent you from travelling, though you might need to plan well in advance. Keeping cool When you start treatment, you will be given a travel bag to make it easier to keep the drugs cool and the syringes safe when you travel. Avonex, Betaferon, Extavia and Copaxone can all be stored at room temperature for a limited amount of time. This ranges from one week to two years. The makers of Rebif have also applied for approval, in 2009, for storing at room temperature. It is recommended that you transfer it to a fridge or equivalent cool place as soon as you reach your destination. In case of delays It might be wise to take a few more doses than you would normally need when you travel in case of unexpected delays. Air travel For air travel, its advisable to keep syringes and drugs in the cabin, rather than in your standard luggage. Temperatures can get extremely low in the baggage hold of an aircraft. The Department for Transport says that syringes are prohibited in hand luggage unless required for medical reasons, and that in general, airport managers and aircraft operators have the discretion to refuse any potential weapon. Rather than risk a problem on the day of travel, it might be sensible to contact both the airport and your individual airline to let them know you will be bringing the medication with you in your hand luggage and ask for any special instructions. For security reasons, the crew may lock them in a special locker in the cabin for the duration of the ight. Ensure you have documentation with you to establish why you need to travel with the drug for example, a letter from your neurologist, MS nurse or GP. The makers of each drug may be able to provide paperwork to help with travel. Channel tunnel If you cross to the Continent using the channel tunnel, you will need to carry with you a letter from your neurologist, MS nurse

15

Disease modifying drugs MS Society 08/09

or GP stating that you need to travel with the drug. At the time of writing, you do not need to tell the travel operator in advance that you will be carrying these items, but its a good idea to always check with them before travelling in case of any changes to the security situation.

Are these treatments vegan-friendly or vegetarian-friendly?

Avonex and Rebif both contain animal products. Betaferon and Extavia do not contain animal product, but contain human serum albumin, a protein found in our blood and produced by the liver. Copaxone is synthetic and does not contain human or animal material. As with other licensed drugs, they have all been tested in animals.

Side effects beta interferon and glatiramer acetate

Most people tolerate these drugs well, but as with any treatment there can be side effects. If you take any of these drugs, you will be monitored to check for side effects. Although Extavia is a new branded drug, it is the same medicine as Betaferon, so the side effect information is the same. Your neurologist or MS nurse can tell you more about the possible side effects covered here, but if you notice unusual or unexpected effects, you should contact them even if you have been taking the drug without problems for some time.

Skin reactions
Betaferon, Copaxone, Extavia and Rebif are all injected under the skin. Disease modifying drugs injected under the skin commonly cause reactions at the site of the injection (reddening, hardening or bruising). Your MS nurse can help you develop good injection technique.

Avoiding injection site problems Good practice includes thorough washing of hands and then cleaning of the skin where you will inject though there is no particular cleaning method recommended for this. Applying an ice pack just before cleaning the skin or after injecting can help reduce painful skin reactions. Also, it is advisable to keep the injecting needle dry avoid discharging any liquid medication onto the outside of the needle before you inject. Allowing the medication to warm to room temperature also helps. Rotating injection sites is important, too, as is injecting where there is sufcient body fat. MS nurse support when you start treatment and throughout your treatment should make injecting manageable.15

16

Disease modifying drugs MS Society 08/09

Less commonly, some people injecting under the skin experience a condition at injection sites called lipoatrophy, in which the fat is lost in small areas under the skin. This leaves dents in the skin, which, if they occur, are usually permanent. The problem can be kept to a minimum by looking out for early signs of dents and avoiding sites which have been affected, rotating injection sites for every injection.

Flu-like symptoms
Avonex, Betaferon, Extavia and Rebif may cause periods of u-like symptoms, such as muscle ache, fever, chills or headache generally for no longer than 48 hours. These are usually worse in the rst three months and lessen over time. Ibuprofen or paracetamol can prevent or improve these symptoms. Injecting immediately before going to bed and taking ibuprofen or paracetamol at that time can alleviate the u-like symptoms you may sleep through the worst of u-like side effects.16 Some people nd drinking more uids on the day of the injection can help reduce the headache.

Changes in menstrual periods

Some women taking Avonex, Betaferon and Rebif experience irregular, early or late periods. If you are concerned, you should ask for a referral to a gynaecologist. This is not a common side effect of these drugs. It affects only around one per cent of people taking them.

Mood changes
Depression is relatively common in people with MS.17 It has been suggested that beta interferon (Avonex, Betaferon, Extavia and Rebif) can make it worse, though it is not certain that this is the case. Before you start on any disease modifying drug, your neurologist or MS nurse will ask if you have been prone to mood changes. If you have been diagnosed with depression in the past, you might not be prescribed beta interferon, though glatiramer acetate may still be a suitable option. This would all be assessed on an individual basis, so having a history of depression does not automatically rule out being prescribed beta interferon.

Neurological symptoms
Rarely, people taking beta interferon experience a are up of their MS symptoms following injection. This normally lasts no more than 48 hours. Some people notice their muscles get stiff during this time. This are up of symptoms could be because the drugs have caused a mild fever many people with MS notice their

17

Disease modifying drugs MS Society 08/09

symptoms get worse when their body temperature rises like this. This side effect, if it occurs at all, usually lessens over the months and years of taking the drug. A few people using glatiramer acetate experience chest pain or tightness immediately following the injection, which can be accompanied by anxiety, ushing, sweating, palpitations or a perceived difculty in breathing. These side effects do not happen often, but can be unpredictable they might happen the rst time someone takes the drug, or after many doses. They usually only last a short time and although unpleasant, these side effects have not been linked to permanent or serious harm. They are not a reason to have to stop taking glatiramer acetate.

Liver function and blood count

Anyone taking beta interferon will have regular blood tests to check liver function and blood cell count. Occasionally, they can cause problems such as mild anaemia, liver abnormalities or a reduction in white blood cell count. Liver abnormalities are actually quite common in people taking these drugs, but are usually mild, settle down on their own and only very rarely mean the person must stop taking the drug.

Other disease modifying drugs

As well as the disease modifying drugs already covered in this booklet which are all licensed for treating MS there are other drugs being researched or already licensed for other conditions. These drugs all aim to affect the course of MS. For more information on any of these (including current trials), and on drugs which can help manage the symptoms of MS, visit the research pages of the MS Society website www.mssociety.org.uk, or call the Information Team 020 8438 0799.

Mitoxantrone
The drug mitoxantrone (brand name Novantrone) is approved in the US for treating secondary progressive MS and worsening relapsing remitting MS (when there is not complete remission between relapses).18 Mitoxantrone is currently licensed in the UK as a cancer-ghting drug. It is not licensed for MS, but it is prescribed for some people with MS (on an individual named patient basis). It is given as a drip, at a hospital. One side effect is that above a certain cumulative dose it can be toxic to the heart, so treatment is limited to courses ranging from six months to two years. Another important side effect is an increased risk of developing a potentially fatal leukaemia. One small study combining mitoxantrone and glatiramer acetate has reported a signicant reduction in relapse rates of 90 per cent and a stabilisation of disability for an average of 36 months.19 A neurologist can explain more fully the potential benets and risks.

18

Disease modifying drugs MS Society 08/09

Azathioprine
The drug azathioprine (Imuran) is sometimes used to help prevent rejection during transplantation and it is also used in a variety of diseases where the immune system is at fault, like MS. Although not licensed for MS, it has been used in MS since the 1960s. There can be a delay in azathioprine having an effect. There are some concerns over side effects.20

IVIg
IVIg (intravenous immunoglobulin) is not a standard treatment for MS. But some neurologists argue that it has a place for reducing the risk of having a relapse in the three months after delivery of a child, when current licensed disease modifying therapies are not considered safe. These potential benets remain unproven.

Alemtuzumab (formerly known as Campath 1H)

This drug is not widely available, but is undergoing large scale clinical trials. Results are expected no sooner than 2012. Alemtuzumab is given by infusion into the blood stream just once a year. Clinical trials with people who had early active relapsing remitting MS have shown it is more effective than beta interferon at reducing relapse rate. In addition, the chance of accumulating disability over three years was reduced by at least 70 per cent compared to people taking beta interferon. It has not been shown to be effective for people with secondary progressive MS. Alemtuzumab is associated with a rare, but serious side effect called ITP (immune thrombocytopenic purpura).21 ITP can be detected through blood test monitoring and then treated.

Rituximab
Rituximab is not licensed for MS, though it is approved to treat certain types of cancer and arthritis. It is given by infusion into the bloodstream. Early clinical trials have shown that people with relapsing remitting MS taking the drug developed fewer brain lesions (signs of MS visible on MRI scans) in the short term. Rituximab has been associated with very serious side effects when used for treating other conditions including PML (a very rare but potentially lethal brain infection).22 A larger trial looking at Rituximab for primary progressive MS is expected to report in 2009.

Fingolimod (FTY720)
Fingolimod (also known as FTY720) is taken as a tablet. It is not licensed. In a large two-year clinical trial, people with relapsing remitting MS had, on average, 52 per cent fewer relapses than those taking beta interferon.23 The manufacturers are expected to apply

19

Disease modifying drugs MS Society 08/09

for a licence in 2009 (meaning it is unlikely to be available for prescription until 2010). A trial involving people with primary progressive MS is underway.

Cladribine
Cladribine is taken as a tablet. It is not licensed, but positive results have recently been presented: in a large two-year clinical trial, people with relapsing remitting MS taking Cladribine had 58 per cent fewer relapses than those taking a dummy treatment.24 The manufacturers are expected to apply for a licence in 2009 (meaning it is unlikely to be available for prescription until 2010).

Further information

MS Society publications The MS Society has publications on a wide variety of topics, including information for people just diagnosed, types of MS, managing relapses, and social care services. For a publications list and order form visit the website www.mssociety.org.uk or call 020 8438 0799 (weekdays 9am-4pm). MS Society website and members magazine Keep up to date with news relating to MS with the MS Society website www.mssociety.org.uk and members magazine, MS Matters. Details about membership are on the website and in the Societys publications list. MS Helpline The award-winning MS Helpline offers condential emotional support and information to anyone affected by MS, including family, friends, carers, newly diagnosed or those who have lived with the condition for many years. Information about MS is available in over 150 different languages by speaking to a Helpline worker via an interpreter. Call freephone 0808 800 8000 (weekdays 9am-9pm, except bank holidays) or email helpline@mssociety.org.uk MS Society National Centre, Information Centre

Disease modifying drugs MS Society 08/09

Based at the MS National Centre in London, the Information Centre is equipped for visitors to read or locate books and journals or view videos and DVDs. To request publications, research articles or other information about MS, visit www.mssociety.org.uk/library or call 020 8438 0799.

20

Local information centres There are MS Society local information and support centres in many locations around the country. These centres are staffed by volunteers who can help you with information about MS and services in your area. Call 020 8438 0799 for the details of your nearest centre. Local branches The MS Society has a network of over 300 local branches across the UK. The branches run by trained volunteers provide information about MS and local services, a chance to meet others affected by MS and take part in a range of activities. For more information check the MS Society website or call 020 8438 0759. www.msdecisions.org.uk Funded by the Department of Health, this online decision tool aims to help people consider whether disease modifying treatment is the right option for them and, if so, which of the available drugs might suit them best.

References
1 Polman C. et al. (2006) A Randomized, Placebo-Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis. New England Journal of Medicine, 354, 899-910. 2 Rudick R. et al. (2006) Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. New England Journal of Medicine, 354, 911-23. 3 Association of British Neurologists (ABN) (2001) Guidelines for the treatment of MS with beta interferon and glatiramer acetate. Available online at www.theabn.org 4 National Institute for Health and Clinical Excellence (2007) NICE technology appraisal guidance 127. Natalizumab for the treatment of adults with highly active relapsing-remitting multiple sclerosis. London, NICE.
Disease modifying drugs MS Society 08/09

5 Clerico, M. et al. (2007) Interferon-beta1a for the treatment of multiple sclerosis. Expert Opinions on Biological Therapy, 7(4), 535-42. 6 Banwell, B. et al. (2006) Safety and tolerability of interferon beta-1b in pediatric multiple sclerosis. Neurology, 66,472-6. 7 Pohl, D. et al. (2005) Treatment of early onset multiple sclerosis with subcutaneous interferon beta-1a. Neurology, 64,888-90.

21

8 Kornek, B. et al. (2003) Glatiramer acetate treatment in patients with childhood and juvenile onset multiple sclerosis. Neuropediatrics, 34(3),120-6. 9 Yousry, T. A. (2006), Evaluation of Patients Treated with Natalizumab for Progressive Multifocal Leukoencephalopathy. New England Journal of Medicine, 354,924-33. 10 Panitch, H. et al. (2005) Benets of high-dose, high-frequency interferon beta-1a in relapsing-remitting multiple sclerosis are sustained to 16 months: nal comparative results of the EVIDENCE trial. Journal of Neurological Science, 239(1), 67-74. 11 Durelli, L. et al. (2006). A randomized study of two interferon-beta treatments in relapsing-remitting multiple sclerosis. Neurology. 67(12), 2264. 12 Mikol D. D. et al. (2008) Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing remitting multiple sclerosis (the Rebif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurology 7(10), 864-6. 13 BEYOND (Betaferon/Betaseron Efcacy Yielding Outcomes of a New Dose) study (2008). Presented by OConnor, P. at the 60th Annual Meeting of the American Academy of Neurology. 14 Hartung H. P. et al. (2007) Neutralising antibodies to interferon beta in multiple sclerosis: expert panel report. Journal of Neurology, 254(7), 827-37. 15 Frohman, E. et al. (2004) Disease modifying agent-related skin reactions in multiple sclerosis: prevention, assessment and management. Multiple Sclerosis, 10, 302-7. 16 Association of British Neurologists (ABN) (2001) Guidelines for the use of beta interferons and glatiramer acetate in multiple sclerosis. Available online at www.theabn.org 17 Arnett, P. A. et al. (2008) Depression in multiple sclerosis: review and theoretical proposal. Journal of the International Neuropsychological Society, 14(5), 691-724. 18 Hartung, H. et al. (2002) Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. The Lancet, 360, 2018-25. 19 Ramtahal, J. et al. (2006) Sequential maintenance treatment with glatiramer acetate after mitoxantrone. Journal of Neurology, September 2006. 253, 1160-4. 20 Palace, J. (2000) Azathioprine. In: C. Hawkins and J. Wolinsky, Principles of Treatments in Multiple Sclerosis, Oxford, Butterworth-Heinemann.

22

Disease modifying drugs MS Society 08/09

21 CAMMS223 Trial Investigators, Coles, A. J. et al. (2008) Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. New England Journal of Medicine, 359(17),1786-801. 22 Hauser, S. L. et al. (2008) B-cell depletion with Rituximab in relapsing remitting multiple sclerosis. New England Journal of Medicine, 358, 676-88. 23 Cohen, J. et al. (2009) Oral ngolimod (FTY720) versus interferon beta-1a in relapsing remitting multiple sclerosis. Results from a phase III study (TRANSFORMS), presented at the American Academy of Neurology 61st Annual Meeting. Abstract S21.004. Presented 29 April, 2009. 24 Giovannoni, G. et al. (2009) Results of the Cladribine Tablets Treating MS Orally (CLARITY) trial, presented at the American Academy of Neurology 61st Annual Meeting. Abstract LBS.001. Presented April 29, 2009.

Authors and contributors

First edition written by Debbie Reeves This edition edited by James Bailey With thanks to Dr Alasdair Coles, Kerry Mutch, the National Hospital for Neurology and Neurosurgery MS Nursing Team, and all those working with and affected by MS who contributed to this booklet. Disclaimer: We have made every effort to ensure that information in this publication is correct. We do not accept liability for any errors or omissions, and policy and practice may change. Seek advice from the sources listed. Suggestions for improvement in future editions are welcomed. Please send them to infoteam@mssociety.org.uk. Multiple Sclerosis Society, 2009 Fourth edition, August 2009

23

Disease modifying drugs MS Society 08/09

MS Society
Multiple sclerosis (MS) is the most common disabling neurological disorder affecting young adults and we estimate that around 100,000 people in the UK have MS. MS is the result of damage to myelin the protective sheath surrounding nerve bres of the central nervous system. This damage interferes with messages between the brain and other parts of the body. For some people, MS is characterised by periods of relapse and remission while, for others, it has a progressive pattern. For everyone, it makes life unpredictable. The MS Society is the UKs largest charity dedicated to supporting everyone whose life is touched by MS. It provides respite care, a freephone MS Helpline, grants for home adaptations and mobility aids, education and training, specialist MS nurses and a wide range of information. Local branches cater for people of all ages and interests and are run by people with direct experience of MS. The MS Society also funds around 80 vital MS research projects in the UK. Membership is open to people with MS, their families, carers, friends and supporters. You can help the work of the MS Society by:

becoming a member making a donation offering your time as a volunteer

Contact information
MS National Centre 372 Edgware Road London NW2 6ND Telephone 020 8438 0700 MS Society Scotland National Ofce Ratho Park 88 Glasgow Road Ratho Station Newbridge EH28 8PP Telephone 0131 335 4050 MS Society Northern Ireland The Resource Centre 34 Annadale Avenue Belfast BT7 3JJ Telephone 028 9080 2802 MS Society Cymru Temple Court Cathedral Road Cardiff CF11 9HA Telephone 029 2078 6676 National MS Helpline Freephone 0808 800 8000 (weekdays 9am-9pm) Website www.mssociety.org.uk The Multiple Sclerosis Society of Great Britain and Northern Ireland is a charity registered in England and Wales (207495) and Scotland (SC016433)
ES06/0809