Multiple sclerosis (MS) treatment intervention with immunomodulating therapy at early disease stage improves short term clinical outcomes. The objective of this study is to describe the long-term outcomes and healthcare utilization of patients with clinically isolated syndrome (CIS) included in the Betaferon®/Betaseron® in Newly Emerging MS for Initial Treatment (BENEFIT) randomized, parallel group trial. In BENEFIT patients were assigned to "early" IFNB-1b treatment or placebo ("delayed" treatment). After 2 years or conversion to clinically definite multiple sclerosis (CDMS), all patients were offered IFNB-1b and were reassessed 15 years later. Of 468 patients, 261 (55.8%) were enrolled into BENEFIT 15 (161 [55.1%] from the early, 100 [56.8%] from the delayed treatment arm). In the full BENEFIT analysis set, risk of conversion to CDMS remained lower in the early treatment group ( - 30.5%; hazard ratio 0.695 [95% CI, 0.547-0.883]; p = 0.0029) with a 15.7% lower risk of relapse than in the delayed treatment group (p = 0.1008). Overall, 25 patients (9.6%; 9.9% early, 9.0% delayed) converted to secondary progressive multiple sclerosis. Disability remained low and stable with no significant difference between groups in Expanded Disability Status Scale score or MRI metrics. Paced Auditory Serial Addition Task-3 scores were better in the early treatment group (p = 0.0036 for treatment effect over 15 years). 66.3% of patients were still employed at Year 15 versus 74.7% at baseline. In conclusion, results 15 years from initial randomization support long-term benefits of early treatment with IFNB-1b.

Amsterdam UMC Location Vrije Universiteit Amsterdam The Netherlands

Bayer AG Berlin Germany

Brain and Mind Center University of Sydney Sydney Australia

CHU Hôpital Pontchaillou Rennes France

Department of Medicine University of Ottawa and The Ottawa Hospital Research Institute Ottawa Canada

Department of Neurology Medical Faculty Heinrich Heine Universität Düsseldorf Germany

Department of Neurology Medical University of Vienna Vienna Austria

Department of Neurology Palacky University in Olomouc Olomouc Czech Republic

Ingress Health HWM GmbH Wismar Germany

Multiple Sclerosis Center of Catalonia Hospital Universitari Vall d'Hebron Barcelona Spain

Queen Square Institute of Neurology and Centre for Medical Image Computing UCL London UK

Research Center for Clinical Neuroimmunology and Neuroscience Basel Departments of Head Organs Spine and Neuromedicine Clinical Research Biomedicine and Biomedical Engineering University Hospital and University of Basel Spitalstrasse 2 4031 Basel Switzerland

UCL Queen Square Institute of Neurology London UK

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