• Ludwig Kappos, Jens Kuhle, Juha Multanen, Marcelo Kremenchutzky, Elisabetta Verdun di Cantogno, Peter Cornelisse, Lorenz Lehr, Florence Casset-Semanaz, Delphine Issard, and Bernard M J Uitdehaag.
• Neurology, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Basel, Switzerland.
• J. Neurol. Neurosurg. Psychiatr. 2015 Nov 1; 86 (11): 1202-7.

AimAn exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) β-1a treatment and other possible prognostic factors with long-term clinical outcomes in relapsing-remitting multiple sclerosis (RRMS).MethodsPatients in the original PRISMS study were invited to a single follow-up visit 15 years after initial randomisation (PRISMS-15). Outcomes over 15 years were compared in the lowest and highest quartile of the cumulative sc IFN β-1a dose groups, and according to total time receiving sc IFN β-1a as a continuous variable per 5 years of treatment. Potential prognostic factors for outcomes were analysed.ResultsOf 560 patients randomised in PRISMS, 291 returned for PRISMS-15 and 290 (51.8%) were analysed. Higher cumulative dose exposure and longer treatment time appeared to be associated with better outcomes on: annualised relapse rate, number of relapses, time to Expanded Disability Status Scale (EDSS) progression, change in EDSS, proportions of patients with EDSS ≥ 4 or ≥ 6, ≤ 5 relapses and EDSS <4 or <6, and time to conversion to secondary-progressive MS (SPMS). Higher dose exposure was associated with lower proportions of patients with EDSS progression and conversion to SPMS, and longer time on treatment with lower risk of first relapse. Change in EDSS from baseline to 24 months was a strong predictor of evaluated clinical outcomes over 15 years.ConclusionsThese findings suggest that higher cumulative exposure to sc IFN β-1a may be associated with better clinical outcomes, and early change in EDSS score may have prognostic value, over many years, in RRMS.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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