• Tomas Kalincik, Eva Kubala Havrdova, Dana Horakova, Guillermo Izquierdo, Alexandre Prat, Marc Girard, Pierre Duquette, Pierre Grammond, Marco Onofrj, Alessandra Lugaresi, Serkan Ozakbas, Ludwig Kappos, Jens Kuhle, Murat Terzi, Jeannette Lechner-Scott, Cavit Boz, Francois Grand'Maison, Julie Prevost, Patrizia Sola, Diana Ferraro, Franco Granella, Maria Trojano, Roberto Bergamaschi, Eugenio Pucci, Recai Turkoglu, Pamela A McCombe, PeschVincent VanVVCliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium., Bart Van Wijmeersch, Claudio Solaro, Cristina Ramo-Tello, Mark Slee, Raed Alroughani, Bassem Yamout, Vahid Shaygannejad, Daniele Spitaleri, José Luis Sánchez-Menoyo, Radek Ampapa, Suzanne Hodgkinson, Rana Karabudak, Ernest Butler, Steve Vucic, Vilija Jokubaitis, Tim Spelman, and Helmut Butzkueven.
• CORe, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia tomas.kalincik@unimelb.edu.au.
• J. Neurol. Neurosurg. Psychiatr. 2019 Apr 1; 90 (4): 458-468.

ObjectiveOral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.MethodsWe identified all patients with relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).ResultsThe eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fumarate (0.20 vs 0.26; p=0.01) and similar on dimethyl fumarate and teriflunomide (0.19 vs 0.22; p=0.55). No differences in disability accumulation (p≥0.59) or improvement (p≥0.14) were found between the therapies. In patients with ≥3-month treatment persistence, subsequent discontinuations were less likely on fingolimod than teriflunomide and dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.68).ConclusionThe effect of fingolimod on relapse frequency was superior to teriflunomide and dimethyl fumarate. The effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment. Persistence on fingolimod was superior to the two comparator drugs.© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

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