OBJECTIVE: Oral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed. METHODS: We 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). RESULTS: The 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). CONCLUSION: The 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.

Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino Avellino Italy

Bologna IRCCS Istituto delle Scienze Neurologiche di Bologna Italy

Central Clinical School Monash University Melbourne Victoria Australia

CHUM and Universite de Montreal Montreal Quebec Canada

CISSS de Chaudière Appalaches Levis Quebec Canada

Cliniques Universitaires Saint Luc Université Catholique de Louvain Brussels Belgium

CORe Department of Medicine University of Melbourne Melbourne Victoria Australia

CSSS Saint Jérôme Saint Jerome Quebec Canada

Department of Basic Medical Sciences Neuroscience and Sense Organs University of Bari Bari Italy

Department of Biomedical and Neuromotor Science University of Bologna Bologna Italy

Department of Emergency and General Medicine Parma University Hospital Parma Italy

Department of Medicine and Surgery University of Parma Parma Italy

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

Department of Neurology ASL3 Genovese and Department of Rehabilitation ML Novarese Hospital Moncrivello Genova Italy

Department of Neurology Box Hill Hospital Monash University Melbourne Victoria Australia

Department of Neurology John Hunter Hospital Hunter New England Health Newcastle New South Wales Australia

Department of Neurology Royal Melbourne Hospital Melbourne Victoria Australia

Department of Neurology The Alfred Hospital Melbourne Victoria Australia

Department of Neuroscience Azienda Ospedaliera Universitaria Modena Italy

Department of Neuroscience Imaging and Clinical Sciences University G d'Annunzio Chieti Italy

Division of Neurology Department of Medicine Amiri Hospital Sharq Kuwait

Dokuz Eylul University Izmir Turkey

Flinders University Adelaide South Australia Australia

Hacettepe University Ankara Turkey

Haydarpasa Numune Training and Research Hospital Istanbul Turkey

Hospital de Galdakao Usansolo Galdakao Spain

Hospital Germans Trias i Pujol Badalona Spain

Hospital Universitario Virgen Macarena Sevilla Spain

IRCCS Mondino Foundation Pavia Italy

Isfahan University of Medical Sciences Isfahan Iran

KTU Medical Faculty Farabi Hospital Trabzon Turkey

Liverpool Hospital Liverpool New South Wales Australia

Medical Faculty 19 Mayis University Samsun Turkey

Monash Medical Centre Melbourne Victoria Australia

Montreal Quebec Hopital Notre Dame Canada

Nehme and Therese Tohme Multiple Sclerosis Center American University of Beirut Medical Center Beirut Lebanon

Nemocnice Jihlava Jihlava Czech Republic

Neuro Rive Sud Quebec City Quebec Canada

Neurologic Clinic and Policlinic Departments of Medicine and Clinical Research University Hospital and University of Basel Basel Switzerland

Rehabilitation and MS Centre Overpelt and Hasselt University Hasselt Belgium

Royal Brisbane and Women's Hospital University of Queensland Brisbane Queensland Australia

School of Medicine and Public Health University Newcastle Newcastle New South Wales Australia

UOC Neurologia Azienda Sanitaria Unica Regionale Marche AV3 Macerata Italy

Westmead Hospital Sydney New South Wales Australia

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Relationship between Patient Preferences, Attitudes to Treatment, Adherence, and Quality of Life in New Users of Teriflunomide

Comparative Effectiveness and Cost-Effectiveness of Natalizumab and Fingolimod in Patients with Inadequate Response to Disease-Modifying Therapies in Relapsing-Remitting Multiple Sclerosis in the United Kingdom