The European Medicines Agency (EMA) has completed its review of the known risk of progressive multifocal leukoencephalopathy (PML) with the multiple sclerosis medicine Tysabri (natalizumab), and has confirmed initial recommendations aimed at minimising this risk.
PML is a rare brain infection caused by John Cunningham (JC) virus. This virus is very common in the general population and is normally harmless; however, it can lead to PML in persons whose immune system is weakened. The most common symptoms of PML are progressive weakness, speech and communication difficulties, vision changes, and sometimes changes in mood or behaviour. PML is a very serious condition that may result in severe disability or death.
Recent studies suggest that early detection and treatment of PML when the disease is asymptomatic (is still in the initial stages and shows no symptoms) may improve patients’ outcomes. Asymptomatic cases of PML can be detected on MRI scans, and experts in the field of MRI and multiple sclerosis agree that simplified MRI protocols (which allow for shorter procedures, and also limit the burden for patients undergoing the scans) permit the identification of PML lesions. All patients taking Tysabri should undergo full MRI scans at least once a year, but on the basis of the new data EMA now recommends that for patients at higher risk of PML more frequent MRI scans (e.g. every 3 to 6 months) performed using simplified protocols should be considered. If lesions suggestive of PML are discovered, the MRI protocol should be extended to include ‘contrast-enhanced T1-weighted MRI’, and testing the spinal fluid for the presence of JC virus should be considered.
New data from large clinical studies also suggest that, in patients who have not been treated with immunosuppressants (medicines that reduce the activity of the immune system) before starting Tysabri, the blood level of antibodies against JC virus (‘antibody index’) relates to the level of risk for PML. In light of the new evidence, patients are considered at higher risk of developing PML if they:
- have tested positive for JC virus, and
- have been treated with Tysabri for more than 2 years, and
- either have used an immunosuppressant before starting Tysabri, or have not used immunosuppressants and have a high JC virus antibody index.
In these patients, treatment with Tysabri should only be continued if benefits outweigh the risks.
If PML is suspected at any time, treatment with Tysabri must be stopped until PML has been excluded.
EMA’s recommendations are based on an initial review by its Pharmacovigilance Risk Assessment Committee (PRAC). The PRAC recommendations were sent to theCommittee for Medicinal Products for Human Use (CHMP), which has now confirmed them and issued its final opinion. The CHMP’s opinion will now be sent to the European Commission for a legally-binding decision valid throughout the EU.