Rituximab dose-dependent infection risk in rheumatoid arthritis is not mediated through circulating immunoglobulins, neutrophils or B cells. (10th June 2022)

• Record Type: Journal Article
• Authors: Opdam, Merel A A; de Leijer, J H; den Broeder, Nathan; Thurlings, Rogier M; van der Weele, Wilfred; Nurmohamed, Michael T; Kok, Marc R; van Bon, Lenny; Ten Cate, David F; Verhoef, Lise M; den Broeder, Alfons A
• Is Part Of: Rheumatology. Volume 62:Number 1(2023)
• Page Start: 330
• Page End: 334
• Publication Date: 2022-06-10
• Subjects: rheumatoid arthritis -- rituximab -- infections -- B cells -- hypogammaglobulinaemia -- mediation analysis; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/keac318
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: Objectives: Rituximab (RTX) is a safe and effective treatment for RA. A dose-dependent infection risk was found in the REDO trial. Some studies associate RTX use with higher infection risks, possibly explained by low immunoglobulin levels and/or neutropenia. Additionally, a higher infection risk shortly after RTX infusion is reported. The objectives of this study were (i) to compare incidence rates of infections between doses and over time, and (ii) to assess B-cell counts, immunoglobulin levels, neutrophil counts and corticosteroid/disease modifying rheumatic drug use as mediating factors between RTX study dose and infection risk. Methods: Post hoc analyses of the REDO trial were performed. Infection incidence rates between RTX dosing groups and between time periods were compared using Poisson regression. A step-wise mediation analysis was performed to investigate if any of the factors mentioned above act as a mediator in the observed dose-dependent difference in infection risk. Results: The potential mediators that were investigated (circulating B-cell counts, immunoglobulin levels, neutrophil counts and drug use) did not explain the dose-dependent infection risk observed in the REDO trial. Additionally, a trend towards a time-dependent infection risk was found, with higher infection rates shortly after RTX infusion. Conclusions: These secondary analyses of the REDO trial confirmed the observed dose-dependent infection risk. Additionally, we found that infection risks were higher shortly after RTX infusion. However, a mediating pathway was not found.