Disease modifying therapies (DMTs) are medications that modify the course of MS and are designed to reduce the number of relapses. Different DMTs affect the number and severity of relapses in varying degrees. 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 DMTs in the same way and people will respond differently. It is important to note that not all side effects will be experienced and sometimes it can take a while to find the right drug for you.
A treatment algorithm was published in 2018 by NHS England, setting out the eligibility criteria for the prescribing of these drugs. It states that treatment should be recommended as soon as the patient becomes eligible.
Patients are eligible if they are showing sustained disability to a level of less than 7.0 on the Expanded Disability Status Scale (EDSS)
People with MS should be managed by a specialist neurologist, who has experience of managing patients with this condition. They should assess your eligibility and suitability for DMTs and should explain the options available to you. You may well have choices over which (if any) you wish to take. Once treatment has started, patients should remain under the supervision of MS specialist neurologists and nurses.
For relapsing remitting MS (RRMS), the current list of licensed DMTs are divided broadly into three classes
Moderately effective
More effective
Highly effective
It is important that if treatment is found to be ineffective, or intolerable side effects are experienced, it should be stopped, under the guidance of your health professional and an alternative offered if possible.
Other reasons for stopping treatment are if secondary progressive MS (SPMS) is confirmed, with the absence of relapse activity.
Pregnancy can also lead to a drug being stopped as many are not suitable to continue use. However, some DMTs may be considered safe or can be used instead of other drugs for an interim period until the original drug can be resumed safely.
For secondary progressive (SPMS) and primary progressive (PPMS), there are also drugs available. Although currently not as many as RRMS, there are many others in development.
Secondary progressive MS (SPMS)
Primary progressive MS (PPMS)
According to the National Institute for Care Excellence (NICE) clinical guidelines for MS, a relapse can be diagnosed by a GP or neurologist if
‘The person with MS has developed new symptoms or has a worsening of existing symptoms, and these symptoms have lasted for more than 24 hours in the absence of infection or any other cause, after a stable period of a least one month.’
Patients with RRMS who have had two or more clinical relapses in the previous two years are considered to have ‘active’ disease which means they are eligible for treatment with a disease modifying therapy. People who have not had any clinical relapses yet show new MRI lesions are also considered for treatment.
All people with active RRMS should be considered for treatment as early as possible. Those with higher levels of disease activity may prefer to start with the more effective drugs.
If a patient is experiencing frequent clinical relapses and/or further MRI activity when either untreated or on a moderately effective drug, they are considered to have more active MS.
To meet the criteria for high disease activity, a person must have had a relapse in the previous year despite taking beta interferon or glatiramer acetate and
a) One or more gadolinium enhancing MRI lesions or b) at least nine T2-hyperintensive lesions on a cranial MRI For patients with more active disease, a highly effective drug is recommended.
Currently, there are no disease modifying therapies recommended in non-relapsing, or non-active SPMS. Some people who experience relapsing SPMS, or ‘active’ SPMS, whereby relapses are present or there is disease activity shown on MRI scans, may be eligible for disease modifying therapy.
In 2020, Mayzent was approved in England to treat ‘active’ secondary progressive MS. It was also approved in 2020 by the Scottish Medicines Consortium (SMC). It is recommended as a treatment option for SPMS, with evidence of active disease in the form of relapses or evidence of inflammation on MRI.
In 2019, Ocrevus was approved in England to treat early-stage, inflammatory PPMS. It was also approved in 2020 by the Scottish Medicines Consortium (SMC). This is the first drug to show evidence in clinical trials to slow down and reduce disability progression in PPMS.
There are several other drugs in development, some of which focus specifically on progressive forms of MS.
Clinically Isolated Syndrome (CIS)
Although not technically a classification of MS, CIS is used to describe 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. 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 DMT.
The NHS England treatment algorithm states that children should be treated using the same guidelines as adults. Children may receive DMTs if they are licensed for children, or if there is a recommended dose for children.
Ideally, children with MS who are aged under 16 should be treated in a specialist clinic with a combined team preferably including adult and paediatric neurologists with a particular interest in MS.
For further information on starting, stopping, or changing a disease modifying therapy please speak to your MS Nurse and/or neurologist.
The National Institute for Care Excellence (NICE) published guidelines in October 2014 for the management of multiple sclerosis (MS). In these guidelines a relapse can be diagnosed by a GP or neurologist if,
‘The person with MS has developed new symptoms or has a worsening of existing symptoms, and these symptoms have lasted for more than 24 hours in the absence of infection or any other cause after a stable period of a least one month.’
How does it work?
Aubagio 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 been shown to have other anti-inflammatory and immune-modulating actions.
How can it help?
Studies showed that Aubagio reduced relapses by one-third. In trials, a higher dose reduced the risk of disability progression (sustained for 12 weeks) by 30 per cent.
How is it administered?
Aubagio is taken as a tablet, once a day.
Who manufactures it?
Genzyme
What type of MS is it prescribed for?
Aubagio is licensed for relapsing remitting MS.
What are the side effects?
Common side effects are gastrointestinal upset, hair thinning and changes in liver function. Aubagio should not be taken by women considering pregnancy because of potential risks to the unborn baby. A woman of child-bearing age considering Aubagio must take a pregnancy test and ensure adequate contraception is in place before starting the drug.
The drug stays in the body for a long time and if a woman taking Aubagio suspects pregnancy, she must immediately contact her GP and, if a pregnancy is confirmed, Aubagio can be ‘flushed out’ of the body by taking activated charcoal or cholestyramine over several days.
Interferons are proteins, produced naturally by the body, that help us fight infection.
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 RRMS. It also reduces the severity of relapses that occur.
Avonex must be injected into the muscle once a week and should be stored in the fridge.
Biogen
Avonex is used in those diagnosed with RRMS.
The most common side effect experienced when taking Avonex is flu-like symptoms after injecting. Injection-site irritations may also occur, such as redness, swelling, itching. Other less common side effects from Avonex can be mood swings, fever and blood abnormalities. Most people find these effects reduce over a three-month period of taking the drug. If they persist, a conversation with an MS nurse or neurologist would be recommended.
Brabio works differently from interferons in that it is a synthetic combination of four amino acids that 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 Brabio is generally reduced by one-third.
It needs to be injected subcutaneously (under the skin). There are two doses, 20mg and 40mg, one is taken as a daily injection and the other is taken three times a week. It needs to be stored in the fridge.
Mylan
Brabio is licensed for RRMS and some people with CIS.
Common side effects are injection-site reactions and lipotrophy (indentations under the skin), chest tightness, headache, anxiety, and nausea. Less common Brabio side effects include thyroid changes, blood cell changes, and palpitations.
Copaxone works differently from interferons in that it is a synthetic combination of four amino acids that 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 one-third.
Copaxone
Copaxone is licensed for RRMS and some people with CIS.
Common side effects are injection-site reactions and lipotrophy (indentations under the skin), chest tightness, headache, anxiety, nausea. Less common side effects include thyroid changes, blood cell changes, and palpitations.
Extavia is thought to block the action of one type of immune cell, called a T-cell, and reduce the autoimmune reaction that causes inflammation and destruction of myelin.
Extavia has been shown to reduce the rate of relapse by about one-third in people with RRMS and reduce the severity of relapses that occur.
Extavia must be injected subcutaneously (under the skin, into body fat) every other day. It does not need to be stored in the fridge.
Extavia – Novartis
Extavia is used in those diagnosed with RRMS. Extavia can also be given to patients with SPMS who show active disease, evidenced by relapses.
The most common side effects experienced with Extavia are flu-like symptoms after injecting and injection-site reactions. It can also cause changes in menstruation, reduced number of white blood cells, headache, and dizziness, however, these symptoms are less common.
Gilenya is an immune-modulating drug, which attaches to the surface of certain white blood cells (known as lymphocytes), causing a number of them to be retained within the body’s immune system.
As a result, fewer lymphocytes get into the bloodstream and fewer reach the central nervous system meaning the potential for an immune attack on the cells of the brain and spinal cord is reduced.
Gilenya was shown to reduce the risk of relapses by 67 per cent compared to a placebo in trials.
It is taken in the form of a capsule, orally, once a day.
Novartis
Gilenya is a ‘more effective’ drug treatment, meaning it has shown to be more effective than injectable therapies. It is licensed for adults with highly active relapsing remitting MS. Such people have a high disease activity, characterised as one relapse in the previous year despite being on another disease modifying therapy, such as an interferon, for at least 12 months.
In June 2014, NHS England published new guidelines to allow a switch to Gilenya for those patients with highly active RRMS, if they met the following criteria
Additionally, in October 2014 the Scottish Medicines Consortium (SMC) licensed Gilenya as a first-line treatment for people with rapidly evolving severe relapsing remitting MS (RES RRMS).
First-line means it can be offered to people with RES RRMS without them having to have taken any previous medication.
Possible side effects include changes to liver function, macularoedema (an accumulation of fluid in the macular area of the eye (the central area of vision) that sometimes causes blurred vision), headache, respiratory tract infection, shortness of breath, diarrhoea and nausea. Gilenya can cause a decrease in heart rate so your first dose will be monitored in hospital for six hours.
Kesimpta is a monoclonal antibody, similar to that of Ocrevus (ocrelizumab). It targets and attaches to specific markers in the immune system called CD20. These form the surface of a type of white blood cell called B cells. It is thought that these B cells are what attack the myelin that surrounds nerve cells and causes the inflammation. Kesimpta targets these B cells and removes them, reducing their overall activity.
Compared to Aubagio (teriflunomide), Kesimpta reduces the risk of relapse by 50 to 59 per cent. Trials showed that people taking this drug had fewer, smaller, or no new areas of active lesions on an MRI scan. It also helps to relieve symptoms and slow down the progression of the disease.
It is suggested Kesimpta is as effective as Lemtrada, Tysabri and Ocrevus.
Kesimpta is self-injected, subcutaneously (under the skin). It is injected weekly for the first three weeks, then you skip a week, before continuing with monthly injections.
It needs to be stored in the fridge and taken out 15 to 30 minutes before injecting to allow it to reach room temperature.
Kesimpta was approved for use in adults with active relapsing remitting MS. It is classed as a highly effective treatment. It can be offered as a first-line drug therapy.
The most common side effects reported for Kesimpta include upper respiratory tract infections, urinary tract infections, injection-related reactions such as fever, headache, muscle pains, and tiredness. Injection-site reactions are also common, such as redness, itching and swelling. These reactions mostly clear up the same day.
Other common side effects include oral herpes, and a reduction in the blood level of immunoglobulins which help to protect against infection.
Lemtrada was originally licensed for the treatment of leukemia. It is a monoclonal antibody which kills T-cells, a type of lymphocyte involved in the MS immune response. Once the T-cells are killed, the immune system repopulates, leading to a modified immune response that no longer regards myelin and nerves as foreign, and therefore stops attacking them.
In two studies, Lemtrada was shown to be effective in reducing the number of relapses in people with relapsing remitting MS. One clinical trial compared Lemtrada to Rebif in people who had not previously been treated with a DMT. Relapses were reduced by 55 per cent compared to Rebif.
In the second trial the drug was again compared to Rebif. In people who had experienced at least one relapse whilst on therapy, Lemtrada reduced the number of relapses by 49 per cent compared to Rebif.
Lemtrada is delivered by two infusions, 12 months apart. The first infusion is delivered over five days, and the second over three days. Infusions take place in a hospital or infusion clinic.
Lemtrada is highly effective when treating more active forms of relapsing remitting MS.
Side effects reported for Lemtrada include one-third of people reporting changes to their thyroid function, which while treatable, can mean lifelong medication is necessary. One per cent of people reported a blood clotting disorder called Immune thrombocytopenic purpura (ITP). While serious, ITP can be treated effectively. Other adverse effects reported relate to kidney function, reactions at the infusion site and respiratory infections.
More common reported side effects were flu-like symptoms after the infusion was given, and some may experience an itchy rash which can be managed by antihistamines.
Mavenclad is an immune-modulating drug that targets specific lymphocytes, T-cells and B-cells.
The drug interferes with DNA synthesis and repair, therefore reducing the number of these lymphocytes. It is these cells that are thought to be involved in the immune response which attacks myelin, causing demyelination.
Studies have shown that Mavenclad reduces relapse rate significantly and delays disability progression by reducing the loss of brain cells, sustained for six months compared with a placebo.
Mavenclad is taken as a tablet. It is taken in two courses, one year apart. The first course is taken over five consecutive days in the first month and over five consecutive days in the second month. The second course is given 12 months later in the same way as the first course. The number of tablets taken in each course is dependent on the individual’s weight.
Merck
Mavenclad is prescribed for people with RRMS. It is listed as ‘more effective’ meaning it is slightly more effective than the injectable therapies.
One of the most common side effects of taking Mavenclad is lymphopenia, which means a reduction in white blood cells. This can increase the risk of getting infections.
Other common side effects include shingles, cold sore, rash, and hair loss. If a patient has shingles, then Mavenclad may need to be stopped until the infection is treated and cleared.
Mayzent is an immune-modulating drug from the same class of drugs as Gilenya. It works by reducing the amount of circulating white blood cells (lymphocytes), preventing them from being able to move freely within the body. Fewer cells are then able to reach the brain and spinal cord, therefore reducing nerve damage caused by SPMS.
Studies have shown that Mayzent helped to slow disability progression by 37 per cent, in those with active SPMS, compared to placebo. In slowing the progression, it also delayed the time to wheelchair dependency in a subgroup of patients, with an EDSS score of 6.5, who were high risk of reaching wheelchair dependency, compared to placebo.
It is to be taken by tablet, once a day.
Tests will be required before starting treatment to determine the correct dosage. This will depend on how well the tablet is broken down in the body.
Mayzent is approved for treating SPMS when there is evidence of disease activity. Either in the form of relapses or inflammatory activity on MRI.
Dosage is increased gradually over the first five days of treatment. This is to reduce the impact on the heart in case of irregular or slowed heartbeat.
Most common side effects from Mayzent include headache, high blood pressure, infections due to lowered white cell count (lymphopenia), visual disturbances.
Ocrevus is a monoclonal antibody that has been designed to target and attach to a specific marker in the immune system called CD20, on the surface of certain types of white blood cells (B cells). These B cells are what attack the immune system and cause inflammation and damage. Ocrevus targets these cells to help reduce their activity.
Studies have shown that Ocrevus can reduce annual relapse by 50 per cent compared to Rebif. Studies also showed that the drug reduced disability progression and reduced the number of lesions shown on MRI when compared with beta interferon. Loss of brain cells was also reduced, and no evidence of disease activity (NEDA) was seen in patients taking Ocrevus, again when compared to Rebif.
Ocrevus is administered by infusion every six months. The initial infusion is given in two separate doses, two weeks apart. After that it is one single dose. Each infusion takes around three to four hours to complete. At the start of each infusion, a corticosteroid and an antihistamine are given to the patient to help prevent any reactions.
Roche
Ocrevus is highly effective when treating more active forms of RRMS. It can only be offered if Lemtrada (alemtuzumab) is contraindicated or unsuitable.
It is also available for those with early PPMS.
Infusion reactions are the most frequently reported side effect (itching, rash and difficulty breathing). They are generally short-lived. Additional medications may be given to prevent this as well as close monitoring during the infusion itself.
Infections are also common, such as chest infections, coughs and colds and herpes virus infections (cold sores or shingles).
Interferons are proteins, produced naturally by the body that help us fight infection.
Plegridy 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 RRMS. It also reduces the severity of relapses that occur.
Plegridy must be injected under the skin every two weeks and should be stored in the fridge.
Plegridy is used in those diagnosed with RRMS.
The most common side effect experienced when taking Plegridy is flu-like symptoms after injecting. Injection-site irritations may also occur, such as redness, swelling, and itching.
Other less common side effects can be mood swings, fever and blood abnormalities. Most people find these effects reduce over a three-month period of taking the drug. If they persist, a conversation with an MS nurse or neurologist is recommended.
Ponvory is an immune-modulating drug. It reduces the amount of circulating white blood cells (known as lymphocytes) and keeps them in the lymph nodes. Fewer cells are then available to attack the myelin sheath. Decreasing nerve damage leads to a reduction in the number of relapses.
Trials show that people taking ponesimod have fewer relapses than those taking teriflunomide. A significant improvement in fatigue was also seen in comparison.
Other trials show that ponesimod taken in a higher dose, showed a 52 per cent reduction in annualised relapse rate, compared to placebo.
It is taken as a tablet, once per day
Janssen
Ponvory is used as a first-line treatment for people with active relapsing remitting MS as defined by MRI. It can also be used as a second line treatment.
Active disease is defined as having one relapse within the last year, or two within the last two years. Or at least one T1 gadolinium enhanced lesion on brain MRI within the last six months.
The most common side effects include the common cold, raised liver enzymes and upper respiratory tract infection.
Other less common side effects include dizziness, headache, vertigo, macular oedema, anxiety.
Like Gilenya, Ponesimod can cause an initial decrease in heart rate. An electrocardiogram (ECG) will be given to check the electrical activity of the heart before the first dose. If there is an increased risk of a slowed heart rate, the first dose will be monitored for up to four hours. An ECG will also be repeated at the end of monitoring.
Rebif blocks the action of one type of protein called gamma interferon. It reduces the autoimmune reaction that causes inflammation and destruction of myelin.
Rebif has been shown to reduce the rate of relapse by about one-third in people with RRMS. It also reduces the severity of relapses that occur .
Rebif must be injected under the skin three times per week and should be stored in the fridge.
Rebif comes in two dosages – 22mcg and 44mcg.
EMD Serono
All types of beta interferon 1a are used in those diagnosed with RRMS
The most common side effect experienced when taking beta interferon 1a is flu-like symptoms after injecting. Injection-site irritations may also occur, such as redness, swelling, and itching.
Other less common side effects can be mood swings (mainly from Avonex), fever and blood abnormalities. Most people find these effects reduce over a three-month period of taking the drug. If they persist, a conversation with an MS nurse or neurologist would be recommended.
It is thought that Tecfidera promotes an anti-inflammatory effect when the immune system attacks myelin, therefore reducing any damage that may be caused to the central nervous system.
Studies have shown that Tecfidera reduces the annual MS relapse rate by around one-half. During trials, MRI scans showed fewer, smaller, or no new active lesions. Some studies also showed a significant reduction in the progression of the disease.
Tecfidera is taken as a tablet, twice a day.
Tecfidera is prescribed for people with relapsing remitting MS. It is listed as ‘more effective’ meaning it is slightly more effective than the injectable therapies.
Common side effects reported are flushing and feeling hot, headaches, gastrointestinal upset and decreased white blood cell count – increasing the risk of infection.
A monoclonal antibody that works in a different way to injectable therapies, Tysabri binds to specific adhesion molecules within the immune cells. This stops the cells from crossing the blood brain barrier and entering the central nervous system, thereby reducing inflammation and damage.
People with RRMS showed a reduction of around two thirds in the number of relapses, fewer MS lesions detected during MRI scans and a significantly reduced rate of disease progression.
In studies, people with RES RRMS showed a decrease of 81 per cent in relapses when taking Tysabri.
Tysabri is administered by intravenous infusion every four weeks at either an infusion centre or a hospital.
Trials suggest Tysabri is as effective when administered every six weeks, lowering the risk of potential side effects. The trial is due to be completed in 2023.
In 2021, Tysabri was authorized for use in injection form. This is to be given as a monthly subcutaneous (under the skin) injection, via a healthcare professional in clinic. Studies show that subcutaneous Tysabri is as effective and safe as intravenous Tysabri.
Tysabri is highly effective when treating more active forms of RRMS.
Side effects can include dizziness, nausea, joint pain, shivering and sometimes inflammation of the nose and throat.
Tysabri increases the risk of developing a serious infection called progressive multifocal leukoencephalopathy (PML), which is a rare but sometimes fatal brain infection that affects the central nervous system. Risk factors associated with an increased risk of PML are the presence of anti-JCV antibodies and the length of time on treatment.
There is a slightly increased risk for patients who remain on the therapy for more than two years. PML is caused by a virus called the John Cunningham virus (JCV).
Each potential patient is tested to check whether they are positive for JCV as this can help to establish the risk of developing PML. As the JCV is airborne, patients can develop it at any time.
This means that patients who test negative for JCV should be retested regularly.
Patients who have been on immune suppressants prior to treatment also have an increased risk factor. Despite these factors, the benefits of the drug continue to outweigh the risks for many people with highly active RRMS.
Vumerity is a similar drug to Tecfidera. It is thought to have an anti-inflammatory effect when the immune system attacks myelin, therefore reducing any damage that may be caused to the central nervous system.
Studies show that Vumerity significantly reduces the amount of active MS lesions on MRI scans. Studies also suggest it reduces relapse rate by the same amount as Tecfidera.
It is taken as a tablet, twice a day.
Vumerity is prescribed for people with RRMS who have moderately active disease in the form of a recent relapse, or new lesions.
Studies show Vumerity is more well-tolerated than Tecfidera with gastrointestinal upset being mild to moderate. It is still one of the more common side effects, but with a lesser impact on daily life.
Other common side effects include flushing, nausea, increased risk of infections.
(Approved for use in Scotland only)
Zeposia belongs to a group of drugs, which work by reducing the amount of circulating white blood cells (lymphocytes), preventing them from being able to move freely within the body. Therefore, reducing inflammation and damage.
Comparison studies with Avonex, show that Zeposia is more effective in reducing the amount of new active lesions on MRI, and reducing brain volume loss. Zeposia was also studied in a higher dose, and this was shown to reduce relapse rate significantly compared to Avonex.
It is taken as a tablet, once a day. The dosage is gradually increased over a period of eight days, to help manage side effects.
Bristol Myers Squibb
Zeposia can be prescribed for people with active RRMS, in Scotland only.
It is currently not recommended by NICE for use in England and Wales.
The most common side effects are an increased risk of infection including coughs, colds, respiratory infection, lowered blood pressure (which will be monitored), slowed heart rate, increased liver enzyme levels.
Once diagnosed with MS, your neurologist will talk to you about any medication you may require and be eligible for. They should 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-to-day living.
There are several factors you may want to consider and discuss with your family and neurologist.
For example
Openly discuss all the options with your MS nurse and/or neurologist to come to a decision on what the best course of treatment is for you.
The MS Trust website has a useful tool called ‘MS Decisions’ with an interactive section that compares the different drugs to help you find the one most suitable for you.
The side effects of these drugs are different with each therapy and vary from person to person. It is important to talk to your MS nurse or neurologist about what side effects the drug may cause. Side effects are generally not severe and there are various ways to manage them.
If you experience 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, providing they do not interfere with any other medication you are taking, it is recommended that you take paracetamol or ibuprofen two hours before the injection to ease the symptoms.
If you have injection-site reactions, you could try using Emla cream which numbs the area prior to the injection. Always rotate the injection site to avoid injecting the same area each time. It may also help to ensure the drug is at room temperature and warming your skin before injecting may also help make your injection more comfortable. If you are on any of the oral therapies, ask your MS nurse how to manage any side-effects you are experiencing.
If the side effects 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 the MS-UK Helpline if you need help to find your nearest MS nurse.
You may be eligible for DMTs, and it is your choice whether you wish to take them or not. Should you choose not to take any medications, this is described as ‘drug naïve’ by health professionals. Your healthcare team may advise you to use DMTs, however, the choice is still yours. If you choose to be drug naïve, it may be useful to keep a symptom diary in case you change your mind in the future.
