Ocrelizumab Leads to Lower Hospitalization Rates Compared to Rituximab in MS

Ocrelizumab (Ocrevus; Genentech) appears to have a more favorable safety profile in patients with multiple sclerosis (MS) compared to rituximab (Rituxan; Genentech and Biogen), according to a new analysis based on real-world data.¹

The findings were published in the Annals of Neurology.

Corresponding author Sergio E. Baranzini, PhD, of the University of California San Francisco (UCSF), and colleagues, explained that the development of anti-CD20 B-cell targeting monoclonal antibodies like rituximab and ocrelizumab has “transformed” clinical practice worldwide.

“The monoclonal antibodies rituximab, ocrelizumab, ofatumumab (Kesimpta), and ublituximab (Briumvi) provide outstanding long-term control against relapsing MS, and ocrelizumab is the only approved therapy against the primary progressive form of the disease,” they wrote.

Yet, while all of the drugs share the same target, the investigators said there remains significant debate over whether their safety and efficacy profiles are similarly comparable.

Baranzini and colleagues noted that rituximab, for instance, is a first-generation chimeric monoclonal antibody, while ocrelizumab is a humanized molecule. The 2 therapies have different mechanisms of action, as well as different molecular structures, immunogenicity, and pharmacokinetics, they added. 

There have already been a small number of studies comparing rituximab and ocrelizumab in MS. One suggested ocrelizumab was more protective against relapses. The other found that patients treated with ocrelizumab for MS and other disorders had a higher seroconversion rate when vaccinated against the SARS-CoV-2 virus, though Baranzini and colleagues noted that that study was highly specific to the context of the pandemic.

Aside from that, while there have been studies looking independently at the safety profiles of individual anti-CD20 B-cell targeting antibodies, there has been a lack of large-scale studies directly comparing their safety profiles.

The investigators decided to use retrospective data from the University of California Health System to simulate a large clinical trial. They created a primary cohort using patients from UCSF and a validation cohort using patients from 5 other University of California Medical Centers. The primary cohort included 542 patients who received ocrelizumab and 271 patients who received rituximab. The validation cohort included 486 patients taking ocrelizumab and 162 patients receiving rituximab.

The data showed that patients taking rituximab had higher rates of all-cause hospitalization compared to those taking ocrelizumab (incidence rate ratio [IRR], 2.29; 95% CI, 1.37-3.82; P = .001 in the UCSF cohort and IRR, 4.54; 95% CI, 4.30-7.61; P < .001 in the UC-wide validation cohort). Cumulative hazard ratios (HRs) were similarly elevated among patients taking rituximab in both cohorts.

The investigators also looked at the risk of developing hypogammaglobulinemia and infection. They found the rate of hypogammaglobulinemia was higher with rituximab in both cohorts (HR, 2.72; 95% CI, 1.18-6.29; P = .003 in the UCSF cohort; HR, 4.79; 95% CI, 2.04-11.25; P < .001 in the UC-wide cohort). The risk of common infections was also elevated in patients receiving rituximab in some instances, though the investigators said the occurrence of infections in the UC datasets was lower than in previous reports, which they said may be the result of patients in that cohort only seeking care if the infections did not self-resolve or were not addressed by non-UC providers.

The investigators noted that some health systems preferentially prescribe rituximab for MS due to its lower cost, among other reasons. However, they said their data show that the safety profiles of the 2 therapies are not identical and that such policies may ultimately result in higher costs due to adverse impacts and hospitalizations. Baranzini and colleagues said future research should aim to understand the biological mechanisms underpinning the apparent safety differences.

References

1. Cerono G, Cree BAC, Hauser SL, Baranzini SE. Comparative safety profiles of ocrelizumab and rituximab in multiple sclerosis treatment using real-world evidence. Ann Neurol. Published online September 8, 2025. doi:10.1002/ana.78033
2. Roos I, Hughes S, McDonnell G, et al. Rituximab vs ocrelizumab in relapsing-remitting multiple sclerosis. JAMA Neurol. 2023;80(8):789-797. doi:10.1001/jamaneurol.2023.1625
3. Nytrova P, Stastna D, Tesar A, et al. Immunity following SARS-CoV-2 vaccination in autoimmune neurological disorders treated with rituximab or ocrelizumab. Front Immunol. 2023;14:1149629. doi:10.3389/fimmu.2023.1149629