Tysabri (natalizumab) is a disease modifying drug (DMD) for very active relapsing remitting MS.
You take Tysabri as an intravenous infusion (drip) once every four weeks to reduce the number and severity of relapses. It reduces the number of relapses by about two thirds (70%).
Common side effects include dizziness, nausea, urticaria (a skin rash) and shivering.
Treatment with Tysabri may increase the risk of progressive multifocal leukoencephalopathy (PML), an uncommon brain infection that can lead to severe disability or even death.
What is Tysabri used for in MS?
Tysabri is a disease modifying drug (DMD) for very active relapsing remitting MS. You have fewer relapses than you might have had with no treatment and any relapses you do have should be less severe.
Tysabri is a highly effective (category 2.0) DMD; in clinical trials, people taking Tysabri had about 70% fewer relapses than people taking placebo. In clinical trials, MRI scans showed that people taking Tysabri had fewer, smaller or no new areas of active MS (lesions). Tysabri may also slow down the build-up of disability associated with MS.
Tysabri can be prescribed if you have very active relapsing remitting MS, which is defined as two or more relapses in one year, with signs of increasing or new lesions between two consecutive MRI scans.
Tysabri has been approved for use on the NHS since 2007. It can only be prescribed by a neurologist.
It is important that you tell your MS team if you have any health problems or are taking other medicines. Your neurologist will need to know if you have previously taken other drugs which suppress the immune system (for example mitoxantrone, azathioprine, cyclophosphamide or methotrexate).
Pregnancy is not recommended during treatment with Tysabri.
If you are trying for a family, your MS nurse or neurologist may recommend remaining on Tysabri until conception, then review whether you should continue treatment during pregnancy based on how active your MS has been and the risk that you might have a significant relapse.
You can take Tysabri as an intravenous infusion (a small tube placed in a vein, with the treatment infused via a pump) once every four weeks. This is generally done in a hospital infusion clinic and takes 2 to 3 hours.
Tysabri can also be taken as an injection given by a health professional once every four weeks. This generally takes place in a hospital clinic and takes less than 1 hour.
You should not stop Tysabri without discussing your ongoing treatment with your neurologist, as your MS may become more active after stopping Tysabri.
What side effects could I get with Tysabri?
Common side effects include dizziness, inflammation of the nose and throat, feeling sick, vomiting, urticaria (a skin rash), shivering and an increased chance of infection. Tysabri may affect liver function but this generally recovers when treatment is stopped.
Treatment with Tysabri may increase the risk of progressive multifocal leukoencephalopathy (PML), an uncommon brain infection that can lead to severe disability or even death. PML is caused by a mutation of the JC virus, a common infection completely unrelated to MS. It is normally kept under control by the immune system, causing no problems. If your immune system is weakened and your body less able to fight an infection, which may occur when taking Tysabri, the JC virus can become active and cause inflammation and damage to the brain.
A blood test can detect the JC virus and give an indication of the risk that you might develop PML. Other factors which increase the risk of PML include previous treatment with an immunosuppressant drug (for example azathioprine, cyclophosphamide, mitoxantrone or methotrexate) and the length of time you have been taking Tysabri. Your neurologist or MS nurse will discuss the implications of the blood test and how it may affect the benefits and risks of treatment.
When you start taking Tysabri you will be informed of the early signs and symptoms of PML. These can be similar to an MS relapse, so it is important to report any new or worsening symptoms. If PML is suspected at any point during treatment, the drug will be discontinued immediately.
Due to the potential risk of side effects, you should be given a patient alert card when you start Tysabri, containing important safety information needed before and during treatment.
Common side effects (affecting more than 1 person in 100)
- urinary tract infections
- inflammation of the nose
- itchy rash (urticaria)
- nausea, vomiting
- joint pain
Less common side effects (affecting less than 1 person in 100)
- severe allergic reaction during infusion (rash, swelling of face, lips or tongue,difficulty breathing)
- discomfort during the infusion including feeling sick, headache, dizziness
- progressive multifocal leukoencephalopathy (PML)
- serious infections
- liver problems
A full list of side effects is included in the manufacturer's Patient Information Leaflet.
Assessment before treatment
Blood tests will be performed before starting treatment to determine whether you have been previously infected by the JC virus. You should have blood and urine tests to measure blood cell counts and to check liver and kidney function. It is also important that you have had a recent (usually within 3 months) MRI scan.
Assessment during treatment
Prior to each infusion, blood pressure, temperature and pulse rate will be taken. Monitoring will also take place during the infusion and for one hour after to check for any serious allergic reaction (hypersensitivity).
If a previous blood test found no evidence of a JC virus infection, you should have further blood tests because it is possible to be infected at any time. If a previous blood test found low levels of JC virus infection, you should continue to have blood tests as the virus level may increase. It is recommended that blood tests are repeated every six months.
If you are at high risk of developing PML, your MS team should consider 3-6 monthly MRI scans as detecting PML early will reduce the likelihood of serious disability.
Further advice has been published for health professionals concerning monitoring for PML.
During the coronavirus outbreak, you may find that your regular blood tests happen less frequently, may take place in a different location or may temporarily stop. The Association of British Neurologists has assessed the risks and benefits of blood monitoring for people taking DMDs, and has recommended a safe minimum schedule during this period. The recommendation for Tysabri is that you should continue to have blood tests and MRI scans, if necessary, every six months. If you notice any new or worsening MS symptoms, you should contact your MS team.
Tysabri binds to immune cells in the blood stream, preventing them from passing from the blood into the central nervous system where they can damage nerves.
Evidence for the effectiveness of Tysabri has come from large clinical trial.
- AFFIRM - Tysabri compared to placebo
This two year study compared Tysabri with placebo in 942 people with relapsing remitting MS.
Tysabri reduced the number of relapses by 68% compared to placebo.
People taking Tysabri were less likely to experience worsening of their disability. After two years, 29% of the placebo group showed at least a one-point increase in the Expanded Disability Status Scale (EDSS), compared to 17% of the Tysabri group.
Tysabri has also been investigated as a treatment for secondary progressive MS where increasing disability is not the result of relapses.
- ASCEND - Tysabri compared to placebo for secondary progressive MS
This phase III trial was designed to test whether Tysabri could slow down the gradual increase in disability experienced by people with secondary progressive MS. The trial involved 889 people with secondary progressive MS who had an EDSS (Expanded Disability Status Scale) score of 6.0 to 6.5 (walking aid needed). Participants took Tysabri or placebo by intravenous infusion (drip) every four weeks for two years. The study measured disability using a combination of EDSS, walking ability and hand and arm function, using the nine hole peg test. Tysabri treatment assessed with the composite disability measure had no effect on the gradual increase in disability. However, looking at hand and arm function separately, Tysabri significantly reduced progression of hand and arm function.
Future research on Tysabri
- AttackMS - Tysabri compared to placebo for clinically isolated syndrome (CIS)
There is strong evidence that starting treatment as soon as possible with a highly effective disease modifying drug gives the greatest potential to delay future disability in MS. However, it can take months, or sometimes even longer, to get a definite MS diagnosis and begin treatment. This study is testing whether it is possible to begin treatment with Tysabri within 14 days of first reporting symptoms typical of MS, also known as clinically isolated syndrome (CIS).
The study aims to recruit 40 people who have at least two MRI lesions suggestive of MS and at high risk of developing MS. Participants will take either Tysabri or placebo for 12 weeks, after which all participants will take Tysabri for a further 12 weeks (24 weeks in total). The main measure of the study will be a measure of remyelination using MRI techniques.
Estimated completion date May 2024
Further details of the study
Participant information sheet
Natalizumab for the treatment of adults with highly active relapsing–remitting multiple sclerosis.
NICE technology appraisal guidance 127.
Full guideline (link is external)
A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.
New England Journal of Medicine 2006; 354: 899-910.
Full article (link is external)
Risk of natalizumab-associated progressive multifocal leukoencephalopathy.
New England Journal of Medicine 2012; 366:1870-1880.
Full article (link is external)
Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension
Lancet Neurol 2018 Mar 12. [Epub ahead of print]
Summary (link is external)