BACKGROUND: The use of non-specific immunosuppressants (NSIS) to treat multiple sclerosis (MS) remains prevalent in certain geographies despite safety concerns, likely due to resource limitations. OBJECTIVE: To use MSBase registry data to compare real-world outcomes in adults with relapsing-remitting MS (RRMS) treated with dimethyl fumarate (DMF) or NSIS (azathioprine, cyclosporine, cyclophosphamide, methotrexate, mitoxantrone or mycophenolate mofetil) between January 1, 2014 and April 1, 2022. METHODS: Treatment outcomes were compared using inverse probability of treatment weighting (IPTW) Cox regression. Outcomes were annualized relapse rates (ARRs), time to discontinuation, time to first relapse (TTFR) and time to 24-week confirmed disability progression (CDP) or 24-week confirmed disability improvement (CDI; in patients with baseline Expanded Disability Status Scale [EDSS] score ≥2). RESULTS: After IPTW, ARR was similar for DMF (0.13) and NSIS (0.16; p = 0.29). There was no difference in TTFR between cohorts (hazard ratio [HR]: 0.98; p = 0.84). The DMF cohort experienced longer times to discontinuation (HR: 0.75; p = 0.001) and CDP (HR: 0.53; p = 0.001), and shorter time to CDI (HR: 1.99; p < 0.008), versus the NSIS cohort. CONCLUSION: This analysis supports the use of DMF to treat patients with relapsing forms of MS, and may have implications for MS practices in countries where NSIS are commonly used to treat RRMS.

American University of Beirut Medical Center Beirut Lebanon

Amiri Hospital Sharq Kuwait

Biogen Baar Switzerland

Biogen Cambridge MA USA

CISSS Chaudière Appalache Lévis QC Canada

Department of Clinical Neuroscience Karolinska Institute Stockholm Sweden

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

Department of Neurology 1st Medical Faculty Charles University Prague and General University Hospital Prague Czech Republic

Department of Neurology Huashan Hospital National Center for Neurological Disorders Fudan University Shanghai China

Department of Neurology University Hospital and University of Basel Basel Switzerland

Dokuz Eylul University Konak Izmir Turkey

Hospital Universitario Virgen Macarena Sevilla Spain

Isfahan University of Medical Sciences Isfahan Iran

KTU Medical Faculty Farabi Hospital Trabzon Turkey

Mayis University Samsun Turkey

Monash University Melbourne Australia

MSBase Foundation Melbourne Australia

Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience Departments of Biomedicine and Clinical Research University Hospital and University of Basel Basel Switzerland

South Eastern HSC Trust Belfast UK

The Alfred Hospital Melbourne Australia

University Hospital Ghent Ghent Belgium

University of Florence Florence Italy

University of Newcastle Newcastle NSW Australia

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