BACKGROUND: To compare the effectiveness and treatment persistence of ocrelizumab, cladribine and natalizumab in patients with relapsing-remitting multiple sclerosis switching from fingolimod. METHODS: Using data from MSBase registry, this multicentre cohort study included subjects who had used fingolimod for ≥6 months and then switched to ocrelizumab, cladribine or natalizumab within 3 months after fingolimod discontinuation. We analysed relapse and disability outcomes after balancing covariates using an inverse-probability-treatment-weighting method. Propensity scores for the three treatments were obtained using multinomial-logistic regression. Due to the smaller number of cladribine users, comparisons of disability outcomes were limited to natalizumab and ocrelizumab. RESULTS: Overall, 1045 patients switched to ocrelizumab (n=445), cladribine (n=76) or natalizumab (n=524) after fingolimod. The annualised relapse rate (ARR) for ocrelizumab was 0.07, natalizumab 0.11 and cladribine 0.25. Compared with natalizumab, the ARR ratio (95% confidence interval [CI]) was 0.67 (0.47 to 0.96) for ocrelizumab and 2.31 (1.30 to 4.10) for cladribine; the hazard ratio (95% CI) for time to first relapse was 0.57 (0.40 to 0.83) for ocrelizumab and 1.18 (0.47 to 2.93) for cladribine. Ocrelizumab users had an 89% lower discontinuation rate (95% CI, 0.07 to 0.20) than natalizumab, but also a 51% lower probability of confirmed disability improvement (95% CI, 0.32 to 0.73). There was no difference in disability accumulation. CONCLUSION: After fingolimod cessation, ocrelizumab and natalizumab were more effective in reducing relapses than cladribine. Due to the low ARRs in all three treatment groups, additional observation time is required to determine if statistical difference in ARRs results in long-term disability differences.

Austin Health Melbourne Victoria Australia

Brain and Mind Centre University of Sydney Sydney New South Wales Australia

Centre integre de sante et de services sociaux des Laurentides point de service de Saint Jerome Saint Jerome Quebec Canada

Clinical Outcomes Research Unit Department of Medicine The University of Melbourne Melbourne Victoria Australia

Cliniques Universitaires Saint Luc Brussels Belgium

Department of Medical and Surgical Sciences and Advanced Technologies GF Ingrassia Catania Italy

Department of Neurology Alfred Hospital Melbourne Victoria Australia

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 Faculty of Medicine Hacettepe University Ankara Turkey

Department of Neurology John Hunter Hospital Newcastle New South Wales Australia

Department of Neurology Royal Melbourne Hospital Melbourne Victoria Australia

Department of Neuroscience Central Clinical School Monash University Melbourne Victoria Australia

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

Departments of Nephrology and Neurology Liverpool Hospital Sydney New South Wales Australia

Division of Neurology Amiri Hospital Sharq Kuwait

Dokuz Eylul University İzmir Turkey

Flinders University Adelaide South Australia Australia

Hôpital Notre Dame CHUM and Universite de Montreal Montreal Québec Canada

Hospital Universitario Virgen Macarena Sevilla Spain

KTU Medical Faculty Farabi Hospital Trabzon Turkey

Menzies Institute for Medical Research University of Tasmania Hobart Tasmania Australia

Multiple Sclerosis Center University of Catania Catania Italy

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

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

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

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De-escalating and discontinuing disease-modifying therapies in multiple sclerosis