Enhanced Safety Profile of Ocrelizumab Over Rituximab in Multiple Sclerosis Treatment
Gabriel Cerono1, Bruce Cree2, Stephen Hauser3, Sergio Baranzini1
1UCSF, 2UCSF, Multiple Sclerosis Center, 3UCSF Weill Institute for Neurosciences
Objective:
Compare long-term safety profiles of ocrelizumab and rituximab in multiple sclerosis (MS) patients using real-world data from multiple specialized MS centers.
Background:
The anti-CD20 monoclonal antibodies ocrelizumab and rituximab have similar mechanisms but differ in molecular structure, epitope target, and cell-killing processes, potentially resulting in unique safety profiles. Despite their broad clinical use in MS, direct comparative data on their long-term safety is lacking.
Design/Methods:
We conducted a multi-center, retrospective observational study, analyzing data from 2,917 MS patients treated with either ocrelizumab or rituximab at six University of California clinical centers. Data from electronic health records were combined with information extracted from unstructured clinical notes using large language models. The primary endpoint was the rate of all-cause hospitalization, while secondary endpoints included infection-related hospitalizations, serum IgG levels, and confirmed disability progression. Propensity score matching was applied to balance cohorts, with follow-up durations of up to 4 years.
Results:
Rituximab-treated patients had significantly higher all-cause cumulative hospitalization compared to ocrelizumab-treated patients (HR 1.93, 95% CI [1.19-3.13], p=0.007) at UCSF; HR 4.01; 95% CI [2.25-6.32], p<0.001) across the UC-wide cohort (Excluding UCSF). Rituximab was also associated with higher infection-related hospitalization rates and a greater likelihood of hypogammaglobulinemia. Ocrelizumab-treated patients showed a trend towards slower disability progression, although not statistically significant. These results remained robust in separate subgroup analyses: one controlling for potential selection bias and another examining the effects among patients on low-dose rituximab regimens.
Conclusions:
This large-scale observational study suggests ocrelizumab has a superior safety profile to rituximab in MS treatment. The significant difference in hospitalization rates and increased hypogammaglobulinemia risk with rituximab may impact clinical practice and healthcare resource use. While these findings cannot replace randomized clinical trials, they provide valuable real-world data to inform MS treatment decisions.
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