OBJECTIVES: The treatment landscape for relapsing-remitting multiple sclerosis (RRMS) is rapidly evolving and it is important for treatment decision-makers and policymakers to have information on the comparative efficacy of RRMS medications. Therefore, we conducted a systematic search to identify clinical trials that have compared the efficacy of FDA-approved disease-modifying therapies (DMTs) versus active comparator medications for the treatment of RRMS.

METHODS: A systematic literature search of PubMed was conducted in December of 2021 to identify phase III clinical trials conducted in the past 10 years in which the efficacy of DMTs versus active comparator medications in the treatment of RRMS was evaluated. The primary efficacy outcome for this assessment was annualized relapse rate (ARR).

RESULTS: Nine phase III clinical trials were identified in which the ~2-year efficacy of FDA-approved DMTs was compared to active comparator medications. Outcomes for infusion DMTs were as follows: ARR was reduced 50% with natalizumab+interferon beta-1a versus injectable interferon beta-1a alone (SENTINEL: 0.34 vs. 0.75); ARR was reduced 55% (CARE-MS-I: 0.18 vs. 0.39) and 49% (CARE-MS-II: 0.26 vs. 0.52) with alemtuzumab versus injectable interferon beta-1a; and with ocrelizumab, ARR was reduced 46% (OPERA-I: 0.16 vs. 0.29) to 47% (OPERA-II: 0.16 vs. 0.29) versus injectable interferon beta-1a. For the oral DMTs, ARR was reduced 21% (RADIANCE low dose: 0.22 vs. 0.28) to 38% (RADIANCE hi dose: 0.17 vs. 0.28) with ozanimod versus injectable interferon beta-1a, and 30.5% with ponesimod versus oral teriflunomide (OPTIMUM: 0.20 vs. 0.29). For the injectable DMT, ofatumumab, ARR was reduced 51% (ASCLEPIOS-I: 0.11 vs. 0.22) to 58% (ASCLEPIOS-II: 0.10 vs. 0.25) versus oral teriflunomide.

CONCLUSIONS: Of the FDA-approved DMTs evaluated in this review, all provided a significant clinical benefit for relapse rate reduction over comparator DMTs. Since comparators differed, further comparison studies, either clinical trials or observational studies, are warranted.