Abstract: Six trials were included and five trials contributed to this review with data. A total of 2904 participants were randomly assigned to IFNs (1704) and GA (1200). The treatment duration was three years for one study, two years for the other four RCTs while one study was stopped early (after one year). The IFNs analysed in comparison with GA were IFN-beta 1b 250 mcg (two trials, 933 participants), IFN-beta 1a 44 mcg (three trials, 466 participants) and IFN-beta 1a 30 mcg (two trials, 305 participants). Enrolled participants were affected by active RRMS. All studies were at high risk for attrition bias. Three trials are still ongoing, one of them completed. Both therapies showed similar clinical efficacy at 24 months, given the primary outcome variables (number of participants with relapse (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.87 to 1.24) or progression (RR 1.11, 95% CI 0.91 to 1.35). However at 36 months, evidence from a single study suggests that relapse rates were higher in the group given IFNs than in the GA group (RR 1.40, 95% CI 1.13 to 1.74, P value 0.002). Secondary magnetic resonance imaging (MRI) outcomes analysis showed that effects on new or enlarging T2- or new contrast-enhancing T1 lesions at 24 months were similar (mean difference (MD) −0.15, 95% CI −0.68 to 0.39, and MD −0.14, 95% CI −0.30 to 0.02, respectively). However, the reduction in T2- and T1-weighted lesion volume was significantly greater in the groups given IFNs than in the GA groups (MD −0.58, 95% CI −0.99 to −0.18, P value 0.004, and MD −0.20, 95% CI −0.33 to −0.07, P value 0.003, respectively). The number of participants who dropped out of the study because of adverse events was similar in the two groups (RR 0.95, 95% CI 0.64 to 1.40). The quality of evidence for primary outcomes was judged as moderate for clinical end points, but for safety and some MRI outcomes (number of active T2 lesions), quality was judged as low. The effects of IFNs-beta and GA in the treatment of people with RRMS, including clinical (e.g. people with relapse, risk to progression) and MRI (Gd-enhancing lesions) measures, seem to be similar or to show only small differences. When MRI lesion load accrual is considered, the effect of the two treatments differs, in that IFNs-beta were found to limit the increase in lesion burden as compared with GA. Evidence was insufficient for a comparison of the effects of the two treatments on patient-reported outcomes, such as quality-of-life measures.

Plain-language summary: Study characteristicsWe searched medical databases for studies in which neither participants nor researchers were told which treatment was given (randomised double-blind trials). The efficacy of the two therapies was considered in terms of occurrence of relapse and progression of disease.Key results and quality of evidenceUp to August 2016, we found six studies comprising 2904 participants (1704 treated with IFNs; 1200 with GA) that met our inclusion criteria requirements. We found that the two therapies seemed to have similar effects or only small differences in the occurrence of relapse or progression.The quality of evidence was moderate overall, although in terms of the safety profile the quality of evidence was low. The risk for incomplete outcome data was found to be high, as some studies present incomplete reporting of adverse events and numbers of participants who dropped out.It is worth noting that all studies but one were sponsored by the drug industry. Furthermore, all of the studies were short-term, with a treatment duration of three years for one study and two years for the other four, while one study was stopped early after one year.