B-cell–depleting anti-CD20 therapies are among the most effective disease-modifying treatments for relapsing–remitting multiple sclerosis (RRMS). Rituximab (RTX) is widely used off-label, while ocrelizumab (OCR) is approved for RRMS; yet comparative real-world evidence between the two remains limited.

We conducted a retrospective registry-based cohort study using the Finnish MS Registry, including adult RRMS patients treated with RTX or OCR between 2018 and 2024 at two university hospitals. Propensity score matching (1:1) was applied to balance baseline characteristics. Primary outcomes were annualized relapse rate (ARR) during follow-up and relapse-free survival. Secondary outcomes included MRI activity, disability progression, adverse events, and longitudinal plasma immunoglobulin G (IgG) levels.

Of 636 screened patients, 191 met inclusion criteria and 112 patients (56 RTX, 56 OCR) were included after matching. Median follow-up was 3.1 years for RTX and 2.6 years for OCR. ARR was low and similar in both groups (mean 0.03), and relapse-free survival did not differ (log-rank p = 0.95; HR 0.95, 95% CI 0.21–4.33). MRI activity remained largely stable, with no significant differences in T2 lesion changes. Adverse events were infrequent and mild. IgG declined modestly in both groups (mean−13%), with values below the reference range in 4.5% of patients and no association with infections. No disease reactivation was observed among patients switching from OCR to RTX.

In this population-based Finnish real-world study, RTX and OCR demonstrated comparable effectiveness and safety in RRMS, supporting RTX as a rational alternative to OCR in routine clinical practice.