Comparative efficacy and safety of ocrelizumab in relapsing-remitting and primary progressive multiple sclerosis: A systematic review and meta-analysis.

OBJECTIVE

This meta-analysis synthesizes evidence from all available randomized trials and observational cohort studies evaluating the efficacy and safety of ocrelizumab compared to placebo or active comparator therapies.

BACKGROUND

Ocrelizumab (OCR), a monoclonal antibody targeting CD20-positive B-cells, is a high-efficacy therapy for multiple sclerosis (MS). While pivotal trials demonstrate its efficacy in reducing relapses, its impact on disability progression and its safety profile in broader, real-world populations require further synthesis.

METHODS

This systematic review and meta-analysis followed PRISMA guidelines and was registered on PROSPERO (CRD420251012243). We searched PubMed, Embase, and Cochrane Central until August, 2025, for randomized controlled trials (RCTs) and observational studies comparing OCR to placebo or active comparators in adults with MS. Primary outcomes were relapse-related measures and confirmed disability progression (CDP); safety outcomes included infections and malignancies.

RESULTS

Twenty-five studies (4 RCTs, 21 observational) were included. OCR was associated with a significant 25% reduction in relapse rates compared to placebo (RR 0.75, 95% CI 0.61-0.93, p = 0.01). However, no significant differences were observed for achieving No Evidence of Disease Activity (NEDA) (RR 1.11, p = 0.13) or CDP (RR 0.90, p = 0.49). Safety analyses revealed no increased risk of overall adverse events, serious infections, or malignancies with OCR. Considerable heterogeneity was observed for several outcomes.

CONCLUSION

This study confirms OCR's significant efficacy in reducing relapse rates and its manageable safety profile in MS. However, its benefits on composite endpoints like NEDA and on halting disability progression remain uncertain and variable, highlighting a need for long-term studies to better define its role in mitigating disease progression.