Comparative effectiveness of ofatumumab and ocrelizumab in relapsing multiple sclerosis: a target trial emulation...

Ofatumumab and ocrelizumab are widely used high-efficacy anti-CD20 therapies for relapsing-remitting multiple sclerosis (RRMS), but direct comparative evidence remains limited. We aimed to compare their effectiveness in routine clinical practice.

We conducted an observational cohort study emulating a target trial using data from the MSBase and Observatoire Français de la Sclérose en Plaques registries (January 2021 to December 2024). Adults with RRMS initiating ofatumumab or ocrelizumab were included. Patients were matched 1:1 using propensity scores. Primary outcomes were annualised relapse rate (ARR) and time to first relapse. Secondary outcomes included time to confirmed disability progression (CDP), progression independent of relapse activity (PIRA), confirmed disability improvement (CDI), MRI activity and treatment discontinuation. Negative binomial and Cox regression models were applied.

A total of 5288 patients were matched with a median follow-up of 1.2 years for ofatumumab and 1.4 years for ocrelizumab. ARR was 0.07 (95% CI 0.05 to 0.08) with ofatumumab and 0.04 (0.03 to 0.05) with ocrelizumab, corresponding to an ARR ratio of 1.75 (1.43 to 2.13). Ofatumumab was associated with a lower risk of CDP (HR 0.66; 0.49 to 0.87) and PIRA (0.53; 0.39 to 0.73), but a lower probability of CDI (0.76; 0.60 to 0.96). No significant differences were observed in MRI activity or treatment discontinuation.

Both therapies were highly effective in a large cohort of patients with RRMS, with very low relapse or CDP rates. Ofatumumab was associated with slightly greater disability control, while ocrelizumab more effectively suppressed relapses. These differences were modest, and their clinical relevance requires further evidence and should be interpreted with caution.