TY - JOUR
T1 - Rituximab dose-dependent infection risk in rheumatoid arthritis is not mediated through circulating immunoglobulins, neutrophils or B cells
AU - Opdam, Merel A. A.
AU - de Leijer, J. H.
AU - den Broeder, Nathan
AU - Thurlings, Rogier M.
AU - van der Weele, Wilfred
AU - Nurmohamed, Michael T.
AU - Kok, Marc R.
AU - van Bon, Lenny
AU - ten Cate, David F.
AU - Verhoef, Lise M.
AU - den Broeder, Alfons A.
N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
PY - 2022/12/23
Y1 - 2022/12/23
N2 - 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.
AB - 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.
KW - Antirheumatic Agents/therapeutic use
KW - Arthritis, Rheumatoid/drug therapy
KW - Humans
KW - Immunoglobulins/therapeutic use
KW - Infections/chemically induced
KW - Neutrophils
KW - Rituximab/therapeutic use
KW - Treatment Outcome
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85144636749&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/35686851
U2 - https://doi.org/10.1093/rheumatology/keac318
DO - https://doi.org/10.1093/rheumatology/keac318
M3 - Article
C2 - 35686851
SN - 1462-0324
VL - 62
SP - 330
EP - 334
JO - Rheumatology (Oxford, England)
JF - Rheumatology (Oxford, England)
IS - 1
ER -