Natalizumab-associated progressive multifocal leukoencephalopathy is not preceded by elevated drug concentrations

作者：van Kempen Zoe L E; Leurs Cyra E; Vennegoor Anke; Wattjes Mike P; Rispens Theo; Uitdehaag Bernard M J; Killestein Joep

来源：Multiple Sclerosis, 2017, 23(7): 995-999.

DOI：10.1177/1352458516684023

<jats:sec><jats:title>Background:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> We investigated the relation between longitudinal natalizumab concentrations in patients who developed PML and patients who did not develop PML. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Our results provide preliminary evidence that contradicts the hypothesis that exposure to elevated concentrations of natalizumab is a relevant risk factor of developing PML. </jats:p></jats:sec>

• 出版日期2017-6