Searches

We identified and examined past relevant systematic reviews, conducted update searches in multiple databases, checked references of included studies, contacted experts in the field, and screened websites for relevant publications. We undertook the main database searches in January and February 2016. These update searches were limited by date to the beginning of 2012 (the year the searches were undertaken for the last comprehensive systematic review and NMA by Filippini et al. [4]) onwards, although we included trials without regard to publication date. This review was chosen because of the breadth of its scope, search strategy and eligibility criteria. A full record of searches is provided in Additional file 1.

We included: a) randomised controlled trials published as full-text reports in English (as well as systematic reviews, or meta-analyses to enable reference checking), b) in people diagnosed with RRMS, c) where the intervention was one of the drugs used within indication at the recommended dosage according to the summary of product characteristics as authorised by the European Medicines Agency (EMA), and d) where the comparator was placebo or best supportive care without DMTs, or another of the interventions when used within indication. Included trials had patient populations primarily comprised of RRMS patients. Our primary outcomes were relapse frequency, disease progression, and discontinuation due to adverse events. Outcomes assessed were relapse rate, time to progression, or discontinuation due to adverse events as outcomes. Full exclusion criteria can be found in the review protocol.