Disease modifying drug therapy What to expect from the hospital-administered drug
Natalizumab (Tysabri)
- What benefits can I expect from this drug?
- Starting treatment
- Administration
- Side effects
- Neutralising antibodies
What benefits can I expect from this drug?
Natalizumab is one of the most recent disease modifying drugs to be approved in the UK for the treatment of multiple sclerosis. Unlike all other disease modifying drugs approved for use in MS, natalizumab is given once every four weeks by infusion in a hospital, clinic or infusion centre.
As discussed in the first section of this book, natalizumab is only approved for use in rapidly evolving severe relapsing remitting MS.
Studies have shown natalizumab to:
- reduce the occurrence of relapses by around two-thirds
- significantly reduce the rate of disease progression
Starting treatment
The assessment process
Appropriateness for treatment with natalizumab needs to be established by a neurologist. The neurologist will look for both clinical and MRI evidence of highly active relapsing remitting MS.
There is limited information on the use of this drug in pregnancy, though animal studies have shown reproductive toxicity. Natalizumab should not be used during pregnancy unless clearly necessary. If you become pregnant while taking natalizumab, inform your neurologist and discontinuation should be considered. It is not known whether natalizumab is excreted in human milk so mothers should not breastfeed whilst they are receiving treatment.
Men who are planning to start a family need to discuss this with their neurologist and MS nurse. Due consideration needs to be given to the practicalities of starting treatment with natalizumab and how it will fit in with your lifestyle. It is important that you are able to attend appointments every four weeks to receive the infusion. The dose and frequency of administration of natalizumab is designed to ensure that optimum levels of the drug remain in the body at all times so it is important that you do not miss a dose.
Checking for other conditions
Blood tests will be performed before you start treatment to determine whether it is safe for you to receive this drug. Before starting on natalizumab you should tell the neurologist if you have any pre-existing conditions or have experienced any reactions to previous drugs or treatments.
Blood tests during treatment
Blood tests will be performed during treatment as part of the monitoring process. Blood samples may be taken to test for the development of neutralising antibodies (see below) and to check levels of liver enzymes.
Administration
How is natalizumab given?
Natalizumab is given as an intravenous infusion (a needle placed in a vein, similar to a drip) once every four weeks. It must be administered in a clinical setting under the supervision of a suitably qualified health professional.
Prior to each infusion, blood pressure, temperature and pulse rates will be taken. A nurse or doctor will monitor the infusion which usually takes one hour and for one hour after the infusion to check for any signs or symptoms of hypersensitivity (allergic) reactions.
What are the side effects?
Natalizumab is designed to treat more active forms of MS and therefore has a more toxic effect in the body. Before starting treatment with natalizumab you will be issued with a patient alert card. The patient alert card is designed to help you identify any potentially serious side effects so they may be addressed in the early stages.
The main side effects associated with natalizumab are:
Infusion reactions
Hypersensitivity (allergic) reactions
Serious infections
Progressive multifocal leukoencephalopathy (PML)
Liver problems
Other less serious side effects
Some people experience some discomfort during the infusion which may include the onset of nausea, headache, itchy rash or dizziness. These tend to be mild and last only as long as the infusion. Around 1 in 5 people who receive natalizumab experience an infusion reaction but it does not affect ongoing treatment with the drug.
Around 1 in 25 people who receive natalizumab experience an allergic reaction. Symptoms of an allergic reaction include itchy rash (hives), swelling of face, lips or tongue, difficulty breathing. Allergic reactions can occur during the infusion or within an hour of completing the infusion where the patient is still under the supervision of the clinical team. Natalizumab is only administered in centres that have the resources for the management of hypersensitivity reactions. People who experience a hypersensitivity reaction to natalizumab must permanently discontinue treatment.
Natalizumab may increase your chance of getting an unusual or serious infection because it can affect your immune system. People receiving natalizumab must alert their health teams if they develop an infection.
This is a rare brain infection that can lead to severe disability or even death. PML is a disorder that usually affects individuals with a weakened immune system. It is a very aggressive condition for which there is no known effective treatment. The symptoms of PML may be similar to an MS relapse so it is important to report any new or worsening symptoms. The estimated risk of developing PML during treatment with natalizumab is about 1 in 1000.
In view of the risks associated with serious infections, particularly PML, individuals undergoing natalizumab treatment are subject to close clinical monitoring.
Liver problems are a rare side effect of natalizumab, affecting less than 1 in 1000. Signs of possible liver problems include yellowing of your skin or the whites of your eyes and unusual darkening of the urine. Blood tests can be done to test for liver damage and where liver damage is detected treatment will be stopped. Liver function generally recovers when treatment is stopped.
A number of other less serious side effects are also associated with natalizumab and are thought to affect fewer than 1 in 10 people receiving the drug. These include: urinary tract infection, sore throat and runny or blocked nose, shivering or fever, itchy rash, headache, dizziness, nausea or vomiting, joint pain and tiredness.
Neutralising antibodies
Antibodies are proteins produced by the immune system to fight foreign substances, such as infections. Sometimes the body's natural defences will develop antibodies against drugs that are entering the body and stop them from working properly. Persistent presence of neutralising antibodies is associated with reduced effectiveness of natalizumab and an increased risk of hypersensitivity reactions. Where the presence of neutralising antibodies is suspected, a blood test may be performed. An individual who tests positive for them will undergo a confirmatory test after six weeks and if the test is positive, treatment will be discontinued.