Natalizumab: risk stratification of individual patients with multiple sclerosis.

At present, three risk factors for the development of progressive multifocal leukoencephalopathy (PML) in natalizumab-treated patients have been identified: the presence of antibodies against JC virus (JCV); the duration of natalizumab treatment, especially if longer than 2 years; and the use of immunosuppressants prior to receiving natalizumab. The most commonly used strategy to assess the individual PML risk includes serum anti-JCV antibody testing. Based on the knowledge on all known risk factors, an algorithm for PML risk stratification has been proposed, where patients with the highest PML risk are those with positive anti-JCV antibodies, treatment duration longer than 2 years, with or without prior history of immunosuppression. These patients would have an approximate incidence of PML of 11.1 (with prior immunosuppression) or 4.6 (without prior immunosuppression) cases per 1,000 patients treated with natalizumab (and treatment duration longer than 2 years). In this review, new data on PML risk factors and possible new strategies for PML risk stratification are discussed.