Zoé LE van Kempen1, Cyra E Leurs1, Anke Vennegoor1, Mike P Wattjes2, Theo Rispens3, Bernard Mj Uitdehaag1, Joep Killestein1. 1. Department of Neurology, Neuroscience Campus Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. 2. Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. 3. Landsteiner Laboratory, Department of Immunology, Sanquin Research, Amsterdam, The Netherlands.
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.
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.
Authors: Michael Auer; Angelika Bauer; Antonia Oftring; Dagmar Rudzki; Harald Hegen; Gabriel Bsteh; Franziska Di Pauli; Klaus Berek; Anne Zinganell; Thomas Berger; Markus Reindl; Florian Deisenhammer Journal: CNS Drugs Date: 2022-09-29 Impact factor: 6.497
Authors: Zoé LE van Kempen; Cyra E Leurs; Birgit I Witte; Annick de Vries; Mike P Wattjes; Theo Rispens; Joep Killestein Journal: Mult Scler Date: 2017-05-09 Impact factor: 6.312