Clinical failure of natalizumab in multiple sclerosis: Specific causes and strategy - 25/06/21

Doi : 10.1016/j.neurol.2021.02.393

D. Guery ^a, R. Marignier ^a,^b,^c, F. Durand-Dubief ^a,^d, C. Lavie ^a, J. Pique ^a, O. Guerrier ^a, S. Vukusic ^a,^c,^e,⁎
^a Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation, hôpital Neurologique Pierre Wertheimer, hospices civils de Lyon, 69677 Lyon/Bron, France
^b Inserm 1028 et CNRS UMR5292, Centre des neurosciences de Lyon, FLUID Team, 69003 Lyon, France
^c Université Claude Bernard Lyon 1, faculté de médecine Lyon Est, 69000 Lyon, France
^d CREATIS, Lyon, France
^e Inserm 1028 et CNRS UMR5292, Centre des neurosciences de Lyon, Observatoire français de la sclérose en plaques, 69003 Lyon, France

^⁎Corresponding author. Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation – hôpital Neurologique Pierre Wertheimer, 59, boulevard Pinel, 69677 Bron cedex, France.Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation – hôpital Neurologique Pierre Wertheimer59, boulevard PinelBron cedex69677France

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Friday 25 June 2021
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Highlights

•	Natalizumab is an effective treatment of MS, with few failures (13% in our study).
•	Every failure needs investigation with a limited number of etiologies to consider.
•	PML, anti-natalizumab antibodies, neuromyelitis optica spectrum disorder (NMOSD) have to be considered in case of inefficacy.

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Abstract

Background

Natalizumab is a very effective treatment of multiple sclerosis (MS). Failure is rare and should lead to consider some specific etiologies. The purpose of our study was to describe causes of subacute neurological events under natalizumab.

Methods

Observational single-center retrospective study in the MS expert center of Lyon, France. Inclusion criteria: any patient with definite MS who received at least three infusions of natalizumab between April 2007 and February 2017. Clinical data were extracted from the Lyon EDMUS/OFSEP database. Events of interest: occurrence of a subacute neurological deficit, characterized by new clinical symptoms. We excluded pseudo-relapses and progression.

Findings

A subacute neurological deficit occurred in 35 cases, for 607 patients treated with natalizumab. Ten patients presented natalizumab antibodies, nine had progressive multifocal leukoencephalopathy (PML), five presented an isolated subacute neurological deficit and two had AQP4 antibodies. No myelin oligodendrocyte glycoprotein (MOG) antibodies were found.

Interpretation

The occurrence of an acute or subacute neurological deficit with natalizumab is rarely a MS relapse and should lead systematically to explore some important alternate etiologies, eliminating PML first.

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Keywords : Multiple sclerosis, Natalizumab, Progressive multifocal leukoencephalopathy, Inefficacy

Abbreviations : AQP4, EDMUS, EDSS, JCV, MS, MOG, MOGAD, NMOSD, OFSEP, PML, SDMT