Disease modifying drug therapy, what you need to know Natalizumab (Tysabri)
Who is eligible for treatment?
Natalizumab (Tysabri) has been used in the UK for the treatment of MS since 2006. National Institute for Health and Clinical Excellence (NICE) and Scottish Medicines Consortium (SMC) guidance recommends prescribing this treatment for a person who experiences two or more disabling relapses in one year, with signs of increasing or new lesions between two consecutive MRI scans. In addition, treatment may be suggested for a person with highly active relapsing MS, who has had at least one relapse in the previous year whilst on treatment with beta interferon, and has shown indication of new or active lesions on an MRI scan.
Before starting treatment, a neurologist will discuss benefits and risks of treatment and a risk education session may be offered. Consideration needs to be given to how treatment will fit with lifestyle, for example the importance of attending appointments every four weeks for infusion. The dose and frequency of administration of natalizumab is to ensure optimum levels of the drug remain in the body at all times, so it is important a dose is not missed. The effects of treatment may start to wear off after about six weeks of stopping.
Assessment before treatment
Blood tests may be performed before treatment commences to determine whether it is safe to receive natalizumab. Assessment of liver function may also form part of this.
The neurologist needs to be informed of any pre-existing conditions, prior exposure to immunosuppressants (for example mitoxantrone, azathioprine) or any reaction to previous drugs or treatments, at this time.
How does natalizumab work?
How is natalizumab given?
Natalizumab is given as an intravenous infusion (a small tube placed in a vein, with the treatment infused via a pump) once every four weeks. The drug is generally administered in an infusion clinic, under the supervision of a qualified health professional.
Prior to each infusion, blood pressure, temperature and pulse rate will be taken. The infusion usually takes one hour. Monitoring will also take place during the infusion and for one hour after, to check for any serious allergic reaction (hypersensitivity).
Benefits of natalizumab
In clinical trials, natalizumab was shown to reduce the relapse rate by 67% in people with relapsing remitting MS. Experience in clinical practice suggests natalizumab may decrease the number of relapses by 81%, reduce the rate of disease progression by approximately two thirds and the accumulation of new MS lesions that are detected using MRI.
Commonly reported side effects of natalizumab include dizziness, nausea, urticaria (a skin rash), stiffness and an increased chance of infection. Natalizumab may affect liver function and this will be monitored during treatment. Liver function generally recovers when treatment is stopped.
|Common (affect more than 1 person in 100)||Less common (affect fewer than 1 person in 100)|
Treatment with natalizumab 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, which is present in about half of the population and normally kept under control by the immune system. If the function of the immune system is weakened and the body is less unable to fight an infection, which may occur with natalizumab, the virus can cause inflammation and damage to the brain.
There is a blood test that can be used to detect the JC virus and helps to identify risk of PML. Other factors which increase the risk of PML include prior treatment with an immunosuppressant drug (for example azathioprine, cyclophosphamide, mitoxantrone or methotrexate) and the length of time a person has been receiving natalizumab. The neurologist or MS specialist nurse will discuss the implications of the blood test and how it may affect the benefits and risks of treatment.
People receiving natalizumab 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.
As the risk of developing PML may change with time, natalizumab treatment is part of an ongoing safety programme which closely monitors and assesses the risk that people being treated with the drug have for developing PML. The risk of developing PML is considered relatively small.
Due to the potential risk of side effects, a patient alert card should be issued with the drug, containing important safety information needed before and during treatment.
Blood tests may be performed during treatment as part of the monitoring process. Annual blood samples may be taken to monitor changes in liver function, the development of neutralising antibodies to the drug and the JC virus.
It is important to discuss any MS relapses during treatment with the neurologist. If the rate and severity of relapses does not improve after six months of treatment, the neurologist will need to consider whether treatment should continue.
Treatment with natalizumab can lead to the development of neutralising antibodies (NAbs). If these neutralising antibodies persist, they may reduce the benefit from treatment and may increase the chance of developing serious allergic (hypersensitivity) reactions.
Most people will not develop neutralising antibodies and in some people they may disappear again over time. A test may be performed if the presence of neutralising antibodies is suspected. A further confirmatory test will be repeated after six weeks. If the neutralising antibodies continue to be present, treatment may have to be discontinued.