Letter Concerning Comparative Safety Profiles of Ocrelizumab and Rituximab in <scp>MS</scp> Treatment

The safety profiles of rituximab and ocrelizumab in multiple sclerosis (MS) were compared in a retrospective observational study recently published in Annals. 1 As rituximab-but not ocrelizumab-was added to the 2023 World Health Organization (WHO) Essential Medicines List for the treatment of MS after a thorough review of existing evidence, some of which was provided by us, we feel obliged to comment on certain inconsistencies.The authors state that "controlled trials of rituximab are limited to a single phase II trial in RRMS" and "Thus, compared to ocrelizumab, there is a paucity of robust evidence from clinical trial data to guide the use of rituximab in the treatment of MS."This is wrong.Rituximab has been compared with dimethyl fumarate in the randomized clinical trial (RCT) setting. 2 The authors also omit reference to other studies that often involve larger study populations and with more careful adjustment for potential confounders than applied here. 3,4urther methodological limitations include the lack of control for calendar effectsgiven the limited temporal overlap between the 2 exposures, and incomplete adjustment for medical history, comorbidities, MS subtype, and sociodemographic factors.These omissions are particularly problematic in light of the conclusions drawn, such as that continued use of rituximab "may ultimately result in increased costs due to higher hospitalization rates and adverse impacts on patient well-being."The authors again fail to refer to existing literature including rigorous cost-effectiveness studies which have demonstrated both improved outcomes including MS-related hospitalizations and substantial reductions in health care expenditures among Black, Hispanic, and White individuals residing in the United States 5 and elsewhere.This conclusion also ignores the spiraling affordability crisis of branded MS treatments such as ocrelizumab, which leave many US patients unable to afford branded disease-modifying therapies (DMTs)a problem that is continuously worsening.Several randomized head-to-head studies comparing rituximab to ocrelizumab are currently ongoing (eg, NCT04688788, NCT05758831, and NCT05834855), the first of which, the Norwegian-Swedish OVERLORD study (NCT04578639), will report top-line results in the coming months.We are confident these studies will succeed in further establishing a robust evidence base for the safety and cost-effectiveness of rituximab in MS, although some resistance is not unexpected.