Natalizumab-associated progressive multifocal leukoencephalopathy is not preceded by elevated drug concentrations. (June 2017)

• Record Type: Journal Article
• Authors: van Kempen, Zoé LE; Leurs, Cyra E; Vennegoor, Anke; Wattjes, Mike P; Rispens, Theo; Uitdehaag, Bernard MJ; Killestein, Joep
• Is Part Of: Multiple sclerosis. Volume 23:Number 7(2017)
• Page Start: 995
• Page End: 999
• Publication Date: 2017-06
• Subjects: Multiple sclerosis -- natalizumab -- progressive multifocal leukoencephalopathy -- natalizumab concentration -- extended dose interval; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458516684023
• Languages: English
• ISSNs: 1352-4585

Abstract

Background: In recent years, a small but increasing number of neurologists choose to extend dose intervals of natalizumab with the aim of reducing the risk of progressive multifocal leukoencephalopathy (PML). This idea is based on the hypothesis that high drug concentrations increase the risk of PML. Objective: We investigated the relation between longitudinal natalizumab concentrations in patients who developed PML and patients who did not develop PML. Methods: In a prospective observational cohort study of 219 patients with relapsing–remitting multiple sclerosis treated with natalizumab, serum samples were taken every 12 weeks prior to natalizumab infusion. In this cohort, 5 patients developed PML and were matched with 10 patients from the cohort who did not develop PML. Natalizumab concentrations were measured in available samples, and the longitudinal results were compared between the two patient groups. Results: Mean natalizumab concentrations in the five patients developing PML was 18.9 µg/mL (standard deviation (SD): ±13.4) versus 23.8 µg/mL (SD: ±11.5) of the control patients. Furthermore, we did not observe a clear rise in concentration levels in patients subsequently developing PML. Conclusion: Our results provide preliminary evidence that contradicts the hypothesis that exposure to elevated concentrations of natalizumab is a relevant risk factor of developing PML.