OBJECTIVES: To evaluate the relative clinical effectiveness of five monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, rituximab, ublituximab) as first-line disease-modifying therapies (DMT) for relapsing forms of multiple sclerosis (MS); and to compare these treatments to placebo and oral DMTs (dimethyl fumarate, fingolimod, ozanimod, ponesimod, and teriflunomide).

METHODS: We systematically identified and reviewed randomized controlled trials (RCTs) of at least one-year duration conducted in adults with relapsing forms of MS. We conducted a Bayesian network meta-analysis (NMA) for the outcomes of annualized relapse rate (ARR) and time to 3-month and 6-month confirmed disability progression (CDP-3/6). Uncertainties were explored with sensitivity analyses.

RESULTS: After a review of 7,100 references, we identified 20 relevant RCTs that met our inclusion criteria, with an additional two RCTs utilized as connecting nodes in the NMA. Monoclonal antibody DMTs were all statistically superior to placebo with an estimated reduction in ARR of ~70% (relative risk range: 0.29 to 0.34). The monoclonal antibodies were generally superior to the oral agents, although the magnitude of the relative differences and statistical significance varied. No statistically significant difference in ARR reduction was observed between the monoclonal antibodies. A similar trend was observed for the CDP- 3 and CDP-6 outcomes; however, there was greater uncertainty in the estimates. Among the monoclonal antibodies, natalizumab, ocrelizumab, and ofatumumab were associated with a reduced risk of CDP-6 versus placebo (hazard ratio range: 0.41 to 0.54). The results of the NMAs were robust to sensitivity analyses.

CONCLUSIONS: Monoclonal antibodies provide substantial benefit relative to placebo for relapses of MS and may provide incremental benefit over the oral agents. The benefits of treatment on CDP-3/6 are less certain. There is insufficient evidence to establish whether there are differences in clinical effectiveness amongst the monoclonal antibodies.