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

Sifat Sharmin, Mathilde Lefort, Johanna Balslev Andersen, Emmanuelle Leray, Dana Horakova, Eva Kubala Havrdova, Raed Alroughani, Guillermo Izquierdo, Serkan Ozakbas, Francesco Patti, Marco Onofrj, Alessandra Lugaresi, Murat Terzi, Pierre Grammond, Francois Grand’Maison, Bassem Yamout, Alexandre Prat, Marc Girard, Pierre Duquette, Cavit BozMaria Trojano, Pamela McCombe, Mark Slee, Jeannette Lechner-Scott, Recai Turkoglu, Patrizia Sola, Diana Ferraro, Franco Granella, Julie Prevost, Davide Maimone, Olga Skibina, Katherine Buzzard, Anneke Van der Walt, Bart Van Wijmeersch, Tunde Csepany, Daniele Spitaleri, Steve Vucic, Romain Casey, Marc Debouverie, Gilles Edan, Jonathan Ciron, Aurélie Ruet, Jérôme De Sèze, Elisabeth Maillart, Hélène Zephir, Pierre Labauge, Gilles Defer, Christine Lebrun-Frénay, Thibault Moreau, Eric Berger, Pierre Clavelou, Jean Pelletier, Bruno Stankoff, Olivier Gout, Eric Thouvenot, Olivier Heinzlef, Abullatif Al-Khedr, Bertrand Bourre, Olivier Casez, Philippe Cabre, Alexis Montcuquet, Abir Wahab, Jean Philippe Camdessanché, Aude Maurousset, Ivania Patry, Karolina Hankiewicz, Corinne Pottier, Nicolas Maubeuge, Céline Labeyrie, Chantal Nifle, David Laplaud, Niels Koch-Henriksen, Finn Thorup Sellebjerg, Per Soelberg Soerensen, Claudia Christina Pfleger, Peter Vestergaard Rasmussen, Michael Broksgaard Jensen, Jette Lautrup Frederiksen, Stephan Bramow, Henrik Kahr Mathiesen, Karen Ingrid Schreiber, Melinda Magyari, Sandra Vukusic, Helmut Butzkueven, Tomas Kalincik, Danish Multiple Sclerosis Registry, OFSEP and the MSBase investigators, Danish Multiple Sclerosis Registry, OFSEP investigators , MSBase Study Group, Ayse Altintas

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1217-1232
Number of pages16
Issue number11
Publication statusPublished - Nov 2021


  • natalizumab
  • Fingolimod
  • relapsing-remitting
  • multiple sclerosis (MS)
  • RRMS
  • EDSS score


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