Comparison of Adverse Event Profiles of Rituximab, Rituximab Hycela and Rituximab Biosimilars: A Real-World Pharmacovigilance Database Analysis

Background: Rituximab is a chimeric monoclonal antibody which targets CD20 and is used for treatment of CD20 associated oncologic/hematologic conditions. Murine-derived variable regions of the antibody contribute to immunogenicity of rituximab products. Clinical trials have shown minor differences in the safety profile of biosimilars and Rituxan-hycela compared to rituximab. Rituxan-hycela and biosimilars were approved recently and real-world adverse drug reaction (ADR) data is lacking.

Methods: We reviewed ADRs of rituximab, Rituxan-hycela and biosimilars between 2018 and 2022 using the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) database. We calculated the reporting odds ratio (ROR) with 95% confidence interval for these drugs.

Results: A total of 39,664 respiratory, dermatological, and immune reactions were noted from Rituximab and its biosimilars. Rituximab/Rituxan had RORs of 5.92 (5.81-6.03), 9.01 (8.84-9.19) and 7.22 (7.07-7.37) in respiratory, skin and immune-related ADRs. Rituximab-hycela had higher odds of causing skin events (ROR 13.25, 9.94-17.68) but had much lesser odds of causing respiratory (ROR 3.34, 1.87-5.97) or immune-related complications (ROR 1.67, 0.86-3.25) compared to rituximab/rituximab-biosimilars. Rituximab-abbs had the lowest odds of causing respiratory (ROR 3.34, 2.90-3.85), skin (ROR 4.80, 4.15-5.55) and immune-related events (ROR 1.76, 1.40-2.22) compared to other biosimilars and rituximab/Rituxan.

Conclusions: Rituximab-abbs showed lower incidence of ADRs in all categories but it is unknown if patients had previously received rituximab. Rituximab-hycela is administered subcutaneously which may explain the lower incidence of respiratory/immune events and higher rate of skin complications. It may be useful in patients at high-risk for allergic reactions to chimeric antibodies. Additional reporting on Rituximab-pvvr and Rituximab-arrx should also exhibit lower reaction rates as compared to Rituximab. Large scale clinical trials are necessary to establish if there is a real difference in ADR rates between different rituximab products.

Master:Cardinal Health: Membership on an entity's Board of Directors or advisory committees; Aptitude health: Membership on an entity's Board of Directors or advisory committees; curio sciences: Membership on an entity's Board of Directors or advisory committees; Blue Bird Bio: Current holder of stock options in a privately-held company; Toxicity: Current holder of stock options in a privately-held company; Gilead: Current holder of stock options in a privately-held company; Jasper: Current holder of stock options in a privately-held company.