Rituximab versus Ocrelizumab in Newly Diagnosed Relapsing Multiple Sclerosis.

Abstract (English)

BACKGROUND: Anti-CD20 monoclonal antibodies are effective for relapsing multiple sclerosis. However, data from head-to-head trials are lacking. METHODS: In this phase 3, multicenter, double-blind, noninferiority trial, we randomly assigned adults with newly diagnosed relapsing multiple sclerosis and recent disease activity in a 3:2 ratio to receive rituximab or ocrelizumab every 6 months for 24 months. The primary end point was the absence of new or enlarging lesions on T2-weighted magnetic resonance imaging (MRI) from month 6 to month 24. Noninferiority was defined as a lower limit of the 95% confidence interval for the risk difference (rituximab minus ocrelizumab) of greater than or equal to -10 percentage points. Secondary end points included efficacy and safety. RESULTS: A total of 218 participants underwent randomization; 216 received treatment (132 assigned to the rituximab group and 84 assigned to the ocrelizumab group). Between months 6 and 24, the estimated probability of having no new or enlarging lesions detected on T2-weighted MRI was 92.2% with rituximab and 94.8% with ocrelizumab, corresponding to a risk difference of -2.6 percentage points (95% confidence interval, -9.4 to 4.3), which met the prespecified noninferiority criterion. Relapse rates, disability outcomes, and cognitive-performance profiles appeared to be similar in the two groups. Infections were more common in the rituximab group than in the ocrelizumab group (in 82% vs. 69% of participants), although the percentage of participants with serious adverse events was similar in the two groups (8% and 7%, respectively). CONCLUSIONS: In participants with newly diagnosed relapsing multiple sclerosis and recent disease activity, rituximab was noninferior to ocrelizumab in suppressing disease activity as detected by MRI from 6 to 24 months, with a similar incidence of serious adverse events. (Funded by the Research Council of Norway and others; OVERLORD-MS ClinicalTrials.gov number, NCT04578639; EudraCT number, 2020-001205-23; EU Clinical Trials Register number, 2024-510716-71-00.).