New EMA Advice to Reduce PML Risk With Natalizumab (Tysabri) in MS

Susan Jeffrey


February 12, 2016

The European Medicines Agency (EMA) today released new recommendations aimed to reduce the risk for progressive multifocal leukoencephalopathy (PML) with use of natalizumab (Tysabri, Biogen) in patients with relapsing remitting multiple sclerosis (MS).

The recommendations come from a review of PML risk associated with natalizumab begun in May 2015 by the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) with the aim of minimizing that risk.

"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) are critically important in limiting the degree of brain damage and resulting disability caused by the disease," an EMA statement released today notes. "Asymptomatic cases of PML can be detected on [a magnetic resonance imaging] scan. On the basis of this data, the PRAC concluded that for patients at higher risk of PML, more frequent [magnetic resonance imaging] scans (e.g. every 3 to 6 months) should be considered."

Known risk factors for the development of PML in patients treated with natalizumab are the presence of antibodies against John Cunningham (JC) virus, treatment with natalizumab for more than 2 years, and treatment with immunosuppressant drugs before starting treatment with natalizumab. Patients who have all three risk factors are considered at higher risk for PML, the statement notes.

New data from clinical studies suggest that in patients who have not been treated with immunosuppressants before starting natalizumab, the JC virus antibody index relates to the level of risk for PML, the EMA writes.

"More specifically, current evidence suggests that the risk of PML is small, and lower than previously estimated, at antibody index values of 0.9 or less, and increases substantially in patients with index values above 1.5 who have been treated with Tysabri for longer than 2 years," the EMA statement notes. "Therefore, the PRAC concluded that patients with a high antibody index who have not used immunosuppressants before Tysabri and have been treated with Tysabri for more than 2 years are also considered at higher risk of PML."

In patients at higher risk of developing PML, treatment with natalizumab should only be continued if the benefits outweigh the risks, it adds.

For those patients with a low antibody index who have not used immunosuppressant drugs before starting natalizumab, the PRAC recommends repeating the antibody test every 6 months, once they have been receiving natalizumab for longer than 2 years.

In patients who test negative for JC antibodies, the antibody test should be repeated every 6 months, the committee recommends. "If PML is suspected at any time, treatment with Tysabri must be stopped until PML has been excluded," the EMA statement notes.

The PRAC recommendation will now be forwarded to the Committee for Medicinal Products for Human Use for the adoption of EMA final opinion. Further details including advice for patients and healthcare professionals will be published at the time of the committee's opinion, the statement concludes.

The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all EU Member States.

In December 2015, the EMA issued advice on minimizing the risk for PML and basal cell carcinoma in patients taking fingolimod (Gilenya, Novartis), and in October 2015, recommendations for reducing PML risk with dimethyl fumarate (Tecfidera, Biogen) in patients with MS.

More information is available on the EMA website.


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