Decrease of natalizumab drug levels after switching from intravenous to subcutaneous administration in patients with multiple sclerosis
Journal of Neurology Neurosurgery & Psychiatry, vol. 94, pp. 482–486
Abstract
BACKGROUND: Natalizumab is effective in the treatment of multiple sclerosis (MS). In 2021, the European Medicines Agency approved the subcutaneous (SC) variant of natalizumab which can be used instead of intravenous administration. However, the course of drug levels varies between administration routes, and the Food and Drug Administration rejected the request for approval of natalizumab SC for reasons that were not disclosed. Our objective was to evaluate the course of natalizumab trough drug levels in patients who switched from natalizumab intravenous to SC on various treatment intervals. METHODS: The NEXT-MS trial (N=382) investigates personalised treatment of natalizumab, in which infusion intervals are prolonged based on individual natalizumab trough drug levels. In 2021, an amendment was approved allowing participants to switch from intravenous to SC administration with frequent measurements of natalizumab drug levels and antidrug antibodies (ADAs). Results were compared with linear mixed model analyses. RESULTS: Until December 2022, 15 participants switched to SC natalizumab. Natalizumab drug levels with SC administration were on average 55% lower compared with intravenous administration (Exp (estimate) 0.45, 95% CI 0.39 to 0.53, p<0.001), leading to very low trough drug levels in three patients on extended treatment intervals. No natalizumab ADAs were detected during intravenous or SC treatment. None of the participants on natalizumab SC showed evidence of MS disease activity. CONCLUSIONS: Natalizumab trough drug levels can decrease after switching from natalizumab intravenous to SC administration. We advise to monitor trough drug levels in patients with low natalizumab drug levels during intravenous treatment, patients with higher body mass index or patients on extended treatment intervals who switch to SC administration of natalizumab.
Authors 15
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Alyssa A Toorop corresponding
Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Neurology, MS Center Amsterdam, Amsterdam UMC Location VUMC, Amsterdam, The Netherlands a.toorop@amsterdamumc.nl
Amsterdam UMC Location VUMC
Department of Neurology, MS Center Amsterdam
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Neurology, MS Center Amsterdam, Amsterdam UMC Location VUMC, Amsterdam, The Netherlands
Amsterdam UMC Location VUMC
Department of Neurology, MS Center Amsterdam
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Affiliation as printed
Biologics Laboratory, Department of Immunopathology, Sanquin Diagnostic Services, Amsterdam, The Netherlands
Biologics Laboratory, Department of Immunopathology
Sanquin Diagnostic Services
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Ommelander Ziekenhuis Groningen
Affiliation as printed
Department of Neurology, Ommelander Hospital Groningen, Scheemda, The Netherlands
Department of Neurology
Ommelander Hospital Groningen
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Affiliation as printed
Department of Neurology, Medical Centre Leeuwarden, Leeuwarden, The Netherlands
Department of Neurology
Medical Centre Leeuwarden
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Affiliation as printed
Department of Neurology, Slingeland Hospital, Doetinchem, The Netherlands
Department of Neurology
Slingeland Hospital
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Elisabeth-TweeSteden Ziekenhuis
Affiliation as printed
Department of Neurology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands
Department of Neurology
Elisabeth-TweeSteden Hospital
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Affiliation as printed
Department of Neurology, Alrijne Hospital, Leiden, The Netherlands
Alrijne Hospital
Department of Neurology
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Affiliation as printed
Department of Epidemiology and Data Science, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Department of Epidemiology and Data Science
Vrije Universiteit Amsterdam
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Neurology, MS Center Amsterdam, Amsterdam UMC Location VUMC, Amsterdam, The Netherlands
Amsterdam UMC Location VUMC
Department of Neurology, MS Center Amsterdam
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Neurology, MS Center Amsterdam, Amsterdam UMC Location VUMC, Amsterdam, The Netherlands
Amsterdam UMC Location VUMC
Department of Neurology, MS Center Amsterdam
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Neurology, MS Center Amsterdam, Amsterdam UMC Location VUMC, Amsterdam, The Netherlands
Amsterdam UMC Location VUMC
Department of Neurology, MS Center Amsterdam
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Neurology, MS Center Amsterdam, Amsterdam UMC Location VUMC, Amsterdam, The Netherlands
Amsterdam UMC Location VUMC
Department of Neurology, MS Center Amsterdam
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Amsterdam UMC Location University of Amsterdam · Sanquin · Amsterdam University Medical Centers
Affiliation as printed
Biologics Laboratory, Department of Immunopathology, Sanquin Diagnostic Services, Amsterdam, The Netherlands
Landsteiner Laboratory, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
Amsterdam UMC Location AMC
Biologics Laboratory, Department of Immunopathology
Landsteiner Laboratory
Sanquin Diagnostic Services
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Neurology, MS Center Amsterdam, Amsterdam UMC Location VUMC, Amsterdam, The Netherlands
Amsterdam UMC Location VUMC
Department of Neurology, MS Center Amsterdam
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