Natalizumab Versus Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Subgroup Analysis From Three International Cohorts

Sifat Sharmin # 1, Mathilde Lefort # 2 3, Johanna Balslev Andersen # 4, Emmanuelle Leray 2 3, Dana Horakova 5, Eva Kubala Havrdova 5, Raed Alroughani 6, Guillermo Izquierdo 7, Serkan Ozakbas 8, Francesco Patti 9 10, Marco Onofrj 11, Alessandra Lugaresi 12 13, Murat Terzi 14, Pierre Grammond 15, Francois Grand'Maison 16, Bassem Yamout 17, Alexandre Prat 18, Marc Girard 18, Pierre Duquette 18, Cavit Boz 19, Maria Trojano 20, Pamela McCombe 21 22, Mark Slee 23, Jeannette Lechner-Scott 24 25, Recai Turkoglu 26, Patrizia Sola 27, Diana Ferraro 27, Franco Granella 28 29, Julie Prevost 30, Davide Maimone 31, Olga Skibina 32 33, Katherine Buzzard 33 34, Anneke Van der Walt 33 34, Bart Van Wijmeersch 35, Tunde Csepany 36, Daniele Spitaleri 37, Steve Vucic 38, Romain Casey 39 40 41 42, Marc Debouverie 43 44, Gilles Edan 45, Jonathan Ciron 46, Aurélie Ruet 47 48 49, Jérôme De Sèze 50, Elisabeth Maillart 51 52, Hélène Zephir 53, Pierre Labauge 54 55, Gilles Defer 56, Christine Lebrun-Frénay 57, Thibault Moreau 58, Eric Berger 59, Pierre Clavelou 60 61, Jean Pelletier 62, Bruno Stankoff 63 64, Olivier Gout 65, Eric Thouvenot 66 67, Olivier Heinzlef 68, Abullatif Al-Khedr 69, Bertrand Bourre 70, Olivier Casez 71, Philippe Cabre 72, Alexis Montcuquet 73, Abir Wahab 74, Jean-Philippe Camdessanché 75, Aude Maurousset 76, Ivania Patry 77, Karolina Hankiewicz 78, Corinne Pottier 79, Nicolas Maubeuge 80, Céline Labeyrie 81, Chantal Nifle 82, David Laplaud 83 84, Niels Koch-Henriksen 85, Finn Thorup Sellebjerg 86, Per Soelberg Soerensen 86, Claudia Christina Pfleger 87, Peter Vestergaard Rasmussen 88, Michael Broksgaard Jensen 89, Jette Lautrup Frederiksen 90 91, Stephan Bramow 92, Henrik Kahr Mathiesen 93, Karen Ingrid Schreiber 86, Melinda Magyari # 4 86, Sandra Vukusic # 40 94 95, Helmut Butzkueven # 33 34 96, Tomas Kalincik # 97 98; Danish Multiple Sclerosis Registry, OFSEP and the MSBase investigators

Affiliations

11 January 2021

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doi: 10.1007/s40263-021-00860-7

Abstract

Introduction: Natalizumab has proved to be more effective than fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Whether this association is universal for all patient groups remains to be determined.

Objective: The aim of this study was to compare the relative effectiveness of natalizumab and fingolimod in RRMS subgroups defined by the baseline demographic and clinical characteristics of interest.

Methods: Patients with RRMS who were given natalizumab or fingolimod were identified in a merged cohort from three international registries. Efficacy outcomes were compared across subgroups based on patients' sex, age, disease duration, Expanded Disability Status Scale (EDSS) score, and disease and magnetic resonance imaging (MRI) activity 12 months prior to treatment initiation. Study endpoints were number of relapses (analyzed with weighted negative binomial generalized linear model) and 6-month confirmed disability worsening and improvement events (weighted Cox proportional hazards model), recorded during study therapy. Each patient was weighted using inverse probability of treatment weighting based on propensity score.

Results: A total of 5148 patients (natalizumab 1989; fingolimod 3159) were included, with a mean ± standard deviation age at baseline of 38 ± 10 years, and the majority (72%) were women. The median on-treatment follow-up was 25 (quartiles 15-41) months. Natalizumab was associated with fewer relapses than fingolimod (incidence rate ratio [IRR]; 95% confidence interval [CI]) in women (0.76; 0.65-0.88); in those aged ≤ 38 years (0.64; 0.54-0.76); in those with disease duration ≤ 7 years (0.63; 0.53-0.76); in those with EDSS score < 4 (0.75; 0.64-0.88), < 6 (0.80; 0.70-0.91), and ≥ 6 (0.52; 0.31-0.86); and in patients with pre-baseline relapses (0.74; 0.64-0.86). A higher probability of confirmed disability improvement on natalizumab versus fingolimod (hazard ratio [HR]; 95% CI) was observed among women (1.36; 1.10-1.66); those aged > 38 years (1.34; 1.04-1.73); those with disease duration > 7 years (1.33; 1.01-1.74); those with EDSS score < 6 (1.21; 1.01-1.46) and ≥ 6 (1.93; 1.11-3.34); and patients with no new MRI lesion (1.73; 1.19-2.51).

Conclusions: Overall, in women, younger patients, those with shorter disease durations, and patients with pre-treatment relapses, natalizumab was associated with a lower frequency of multiple sclerosis relapses than fingolimod. It was also associated with an increased chance of recovery from disability among most patients, particularly women and those with no recent MRI activity.

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