OBJECTIVE: B-cell-depletion via CD20 antibodies is a safe and effective treatment for active relapsing multiple sclerosis (RMS). Both ocrelizumab (OCR) and ofatumumab (OFA) have demonstrated efficacy in randomized controlled trials and are approved for treatment of RMS, yet nothing is known on their comparative effectiveness, especially in the real-world setting.

METHODS: This prospective cohort study includes patients that were started on either OCR or OFA between September 2021 and December 2023. Patients were followed until June 2024 and recruited at 3 large tertiary centers in Germany (Duesseldorf, Essen, and Giessen). Propensity-score-matching was used to address baseline imbalances among patients. Clinical relapses, presence of new or enlarging MRI lesions and 6-month confirmed disability worsening were evaluated. Non-inferiority of OFA compared to OCR was evaluated through comparison of Kaplan-Meier-estimates.

RESULTS: A total of 1,138 patients were initially enrolled in the cohort. Following patient selection and propensity-score-matching, 544 OCR and 417 OFA patients were included in the final analysis. In our primary analysis, OFA was non-inferior to OCR in terms of relapses, disability progression, and accrual of MRI lesions. Subgroup analyses confirmed findings in previously naïve and platform-treated patients. Potential differences between OFA and OCR were seen in patients switching from S1P receptor modulators or natalizumab.

CONCLUSION: We here provide comparative data on the effectiveness of OCR and OFA in patients with active RMS. OFA was non-inferior to OCR in the overall cohort. Potential differences observed in patients switching from S1P receptor modulators or natalizumab require further validation. ANN NEUROL 2025;97:583-595.