Clinical failure of natalizumab in multiple sclerosis: Specific causes and strategy

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 multi-focal 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. (C) 2021 Published by Elsevier Masson SAS.