Comparative Safety Profiles of Ocrelizumab and Rituximab in Multiple Sclerosis Treatment Using Real-World Evidence.

Abstract

The objective of this study was to compare the long-term safety profiles of ocrelizumab and rituximab in persons with multiple sclerosis (MS). Using retrospective data from the University of California (UC) Health System, we simulated a target clinical trial. The primary cohort from UC San Francisco (UCSF) and a validation cohort from 5 other UC Medical Centers were analyzed. After applying exclusion criteria and propensity score matching based on disease characteristics, demographics, and socioeconomic factors, we compared UCSF patients receiving ocrelizumab (n = 542) and rituximab (n = 271)and validated in the UC-wide MS population (n = 486 and n = 162 patients, respectively). The primary outcome was an all-cause hospitalization rate; secondary outcomes included hypogammaglobulinemia development and infection incidence. Rituximab showed higher all-cause hospitalization rates compared to ocrelizumab in both UCSF (incidence rate ratio [IRR] = 2.29, 95% confidence interval [CI] = 1.37-3.82, p = 0.001) and UC-wide cohorts (IRR = 4.54, 95% CI = 4.30-7.61, p < 0.001). Cumulative hazard ratios (HRs) were similarly elevated with rituximab at UCSF (HR = 2.27, 95% CI = 1.37-3.75, p = 0.001) and UC-wide (HR = 4.01, 95% CI = 2.25-6.32, p < 0.001). The risk of developing hypogammaglobulinemia was higher with rituximab at both UCSF (HR = 2.72, 95% CI = 1.18-6.29, p = 0.003) and UC-wide (HR = 4.79, 95% CI = 2.04-11.25, p < 0.001). A more favorable safety profile was observed for ocrelizumab, with lower rates of hospitalization and hypogammaglobulinemia across 2 independent cohorts. These findings may help guide treatment strategies in persons with MS. ANN NEUROL 2026;99:248-260.