Comparative efficacy and safety of disease-modifying therapies in patients with relapsing multiple sclerosis: A systematic review and network meta-analysis

Abstract

Background

Currently, 19 disease-modifying therapies (DMTs) have been approved for the treatment of patients with relapsing forms of multiple sclerosis (RMS). The objective of this study was to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of DMTs in adults with RMS.

Methods

We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) websites for randomized controlled trials (RCTs) (from inception to July, 2021). Eligible RCTs evaluated approved treatments for RMS as monotherapy, report at least one of the primary outcome measures of interest. The primary outcome was efficacy (annualized relapse rate and 12-week confirmed disability progression) and safety (serious adverse events and discontinuation due to adverse events). We assessed the risk of bias of included studies using the Cochrane risk-of-bias tool (RoB) V.2.0 tool for RCTs. Surface under the cumulative ranking (SUCRA) was used to rank therapies and to assess quality of general evidence, respectively. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework were used to rank therapies and to assess quality of general evidence.

Results

43 records represent 45 RCTs selected for network meta-analysis. In total, 30,720 participants (median of 732; interquartile range: 248-931) were included, of which 67% were female. By SUCRA analysis, alemtuzumab (94.3%) presented the highest probability of being the best alternative for annualized relapse rate (ARR), while ofatumumab (93.5%) presented the highest probability of being the best alternative for 12-week confirmed disability progression. Interferon beta-1b subcutaneous (87.0%) presented the highest probability of the best safety among all DMTs for serious adverse events, while alemtuzumab (92.4%) presented the highest probability of the best safety among all DMTs for discontinuation due to adverse events.

Conclusion

Network meta-analysis shows that alemtuzumab and ofatumumab present the highest efficacy among DMTs. Since there is little difference between these probabilities for many treatments, health professionals should use clinical shared decision making when formulating treatment plans with patients.