BACKGROUND: There is growing interest in the issue of disease reactivation in multiple sclerosis following fingolimod cessation. Relatively little is known about modifiers of the risk of post-cessation relapse, including the delay to commencement of new therapy and prior disease activity. OBJECTIVE: We aimed to determine the rate of relapse following cessation of fingolimod and to identify predictors of relapse following cessation. METHODS: Data were extracted from the MSBase registry in March 2019. Inclusion criteria were (a) clinically definite relapsing multiple sclerosis, (b) treatment with fingolimod for ≥ 12 months, (c) follow-up after cessation for ≥ 12 months, and (d) at least one Expanded Disability Status Scale score recorded in the 12 months before cessation. RESULTS: A total of 685 patients were identified who met criteria. The mean annualised relapse rate was 1.71 (95% CI 1.59, 1.85) in the year prior to fingolimod, 0.50 (95% CI 0.44, 0.55) on fingolimod and 0.43 (95% CI 0.38, 0.49) after fingolimod. Of these, 218 (32%) patients experienced a relapse in the first 12 months. Predictors of a higher relapse rate in the first year were: younger age at fingolimod cessation, higher relapse rate in the year prior to cessation, delaying commencement of new therapy and switching to low-efficacy therapy. CONCLUSIONS: Disease reactivation following fingolimod cessation is more common in younger patients, those with greater disease activity prior to cessation and in those who switch to a low-efficacy therapy.

Box Hill Hospital Melbourne VIC Australia

Central Clinical School Monash University Melbourne VIC Australia

CISSS ChaudiËre Appalache Levis QC Canada

Department of Medicine CORe University of Melbourne Melbourne VIC 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 Box Hill Hospital Monash University Melbourne VIC Australia

Department of Neurology John Hunter Hospital Hunter New England Health Newcastle NSW Australia

Department of Neurology Royal Melbourne Hospital Melbourne MS Centre Melbourne VIC Australia

Department of Neurology The Alfred Hospital Melbourne VIC Australia

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

Division of Neurology Department of Medicine Amiri Hospital Sharq Kuwait

GF Ingrassia Department University of Catania Catania Italy

Hospital Universitario Virgen Macarena Sevilla Spain

L4 Centre Melbourne Brain Centre at Royal Melbourne Hospital Grattan Street Parkville VIC 3050 Australia

Liverpool Hospital Sydney NSW Australia

Monash University Melbourne VIC Australia

Policlinico G Rodolico Catania Italy

Royal Melbourne Hospital Melbourne MS Centre Melbourne VIC Australia

School of Medicine and Public Health University of Newcastle Newcastle NSW Australia

The Alfred Hospital Melbourne VIC Australia

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