Know one you know them all? Are the CD20-depleting antibodies all the same?. You would think so, as they all deplete CD20 positive B cells but this study says that rituximab causes more infections than ocrelizumab.
The weird thing is other people are saying that ocrelizumab is better than rituximab based on MSbase.
Roos I, Hughes S, McDonnell G, Malpas CB, Sharmin S, Boz C, Alroughani R, Ozakbas S, Buzzard K, Skibina O, van der Walt A, Butzkueven H, Lechner-Scott J, Kuhle J, Terzi M, Laureys G, Van Hijfte L, John N, Grammond P, Grand’Maison F, Soysal A, Jensen AV, Rasmussen PV, Svendsen KB, Barzinji I, Nielsen HH, Sejbæk T, Prakash S, Stilund MLM, Weglewski A, Issa NM, Kant M, Sellebjerg F, Gray O, Magyari M, Kalincik T; MSBase Study GroupDanish MS Registry Study Group. Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis. JAMA Neurol. 2023;80:789-797.
Ocrelizumab are very similar in terms of their target they bind to a very similar area of the large loop of CD20. One is chimeric and the other is humanized meaning it is slightly less antigenic.
Ocrelizumab exhibits slightly reduced complement fixation compared to rituximab which can lead to potentially lower risks of infusion reactions, though both are effective anti-CD20 therapies that rapidly deplete B cells in the peripheral blood. While rituximab relies more on complement fixation (uses complement to punch holes in cells) ocrelizumab’s depletion mechanism is more weighted towards antibody dependent cellular cytotoxicity (used perferoins from cells to punch holes in cells).
There are some bacteria that are preferentially removed by complement dependent mechansisms and perhaps could reliy of this to get rid of them,
Ocrelizumab can kill B cells perhaps better than rituximab but the main difference is the amount injected and people with rituximab get a third more…..so it must penetrate tissues more and proabably depletes B cells more and you need T and B cells to fight infection. it drops antibody three times more than ocrelizumab so if depletes B cells better and so it may cause more infections. Does it protect against MS better? You can’t have it both ways so suggests the Swedes are happy with their choice. But the ocrelizumab is better than rituximab according to information above. I await the head-to head trial result that is ongoing it should have completed around now
Ocrelizumab VErsus Rituximab Off-Label at the Onset of Relapsing MS Disease (OVERLORD-MS) (NCT04578639) will it be rituximab’s D-day
COI: The authors play down any perceived conflicts.
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. 2025 . doi: 10.1002/ana.78033.
Objective: The objective of this study was to compare the long-term safety profiles of ocrelizumab and rituximab in persons with multiple sclerosis (MS).
Methods: 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.
Results: 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).
Interpretation: 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 2025.
Source: multiple-sclerosis-research.org