Risk stratification of progressive multifocal leukoencephalopathy under natalizumab

JC virus (JCV)-associated progressive multifocal leukoencephalopathy (PML) represents a rare but serious side effect of natalizumab (TysabriA (R)) in the treatment of patients with relapsing forms of multiple sclerosis (MS). Two factors that may increase the risk of PML have been identified: treatment duration beyond 24 months and prior immunosuppressive therapy. Recently determination of anti-JCV antibodies mirroring JCV infection has allowed a third factor to be added to this list, and a positive serological test has been included as a risk factor on the label of natalizumab. Clearly, JCV serology represents a tool for PML risk stratification in MS patients treated with natalizumab. However, current data as well as the experimental development of the underlying assay have not been validated by an independent laboratory. The present article discusses possibilities and challenges of this assay and, based on our present knowledge, provides recommendations for the clinical implementation in daily practice.