• Julian Borchardt and Joseph R Berger.
• An Independent Statistical Consultant in Germany. Electronic address: julian.borchardt@gmx.de.
• Mult Scler Relat Disord. 2016 Jul 1; 8: 145-50.

ObjectiveTo estimate the prospective risk of developing PML during therapy with natalizumab in JCV-seropositive patients.MethodsWe analyzed postmarketing data about the incidence of PML on natalizumab, and quantified the risk by either applying the Kaplan-Meier estimator or, where this was not possible due to the unavailability of the respective raw data, using formulae yielding very similar figures.ResultsIn JCV-seropositive patients with prior immunosuppressant (IS) use, the incidence of PML during months 25-48 of natalizumab therapy is about 19.5 per thousand. Without prior IS use, the incidence during months 25-48 is approximately 7.4 per thousand, and during months 49-72, it is approximately 10.8 per thousand. If one additionally assumes that the JCV index is in the range 0.9-1.5, then the incidence during months 49-72 is around 6.2 per thousand in comparison to 17.0 per thousand when the JCV index exceeds 1.5.ConclusionsBiogen's statistics concerning the risk of PML on natalizumab, while in principle helpful, underestimate the true incidence systematically and significantly; realistic estimates of the longterm risk of PML are nearly double those previously published, with some patient groups carrying a risk that is almost nine times higher. Fortunately, a refined risk-stratification algorithm with the incorporation of such markers as L-selectin and CSF lipid-specific IgM bands has the potential to make natalizumab a considerably safer drug.Copyright © 2016 Elsevier B.V. All rights reserved.

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