Identification of Covariates Modulating B‐Cell Repopulation Kinetics in Subjects Receiving Rituximab Treatment

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 75; no. 11; pp. 2045 - 2053
• Main Authors: Welte, Thomas, Westermann, Lukas, Kappes, Julia, Schramm, Markus A., Bemtgen, Xavier, Staudacher, Dawid L., Hug, Martin J., Venhoff, Nils, Arnold, Frederic
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2023
• Subjects: Age; Antineutrophil cytoplasmic antibodies; Autoimmune diseases; Azathioprine; CD20 antigen; Corticoids; Corticosteroids; Cyclophosphamide; Cyclosporins; Depletion; Dosage; Health risks; Hydroxychloroquine; Immunosuppression; Immunotherapy; Kidneys; Kinetics; Methotrexate; Monoclonal antibodies; Mycophenolate mofetil; Mycophenolic acid; Observational studies; Regression analysis; Regression models; Repopulation; Risk management; Rituximab; Steroids; Tacrolimus; Transplantation; Vasculitis
• DOI: 10.1002/art.42625
• ISSN: 2326-5191; 2326-5205

Effective B-cell depletion using the anti-CD20 monoclonal antibody rituximab is a cornerstone in the therapeutic concept of multiple autoimmune diseases. B-cell depletion is associated with a higher risk for severe infections and the timespan of B-cell repopulation differs greatly between individuals. Data on factors influencing B-cell repopulation kinetics are limited. This study aims to identify patient-specific and therapy-associated covariates that modulate B-cell repopulation. This single-center retrospective observational study presents data of 839 subjects receiving 2,017 courses of anti-CD20 antibody rituximab for auto-immune disease. Assessed covariates are patient-specific factors (sex, age, kidney function and underlying disease) and co-immunosuppression with common agents (azathioprine, cyclosporine A, cyclophosphamide, hydroxychloroquine, methotrexate, mycophenolate mofetil, tacrolimus and corticosteroids). The primary endpoint is the time to B-cell repopulation (CD19 cells ≥ 5/μl). The secondary endpoint is the time to B-cell reconstitution (CD19 cells ≥ 50/μl). Multivariate time-to-event analysis and logistic regression models were applied to estimate the influence of covariates. Age > 60 years (HR 0.71 for repopulation, P = 0.008), impaired kidney function (HR 0.72, P = 0.001), AAV (HR 0.61, P < 0.001), solid organ transplantation (HR 0.4, P < 0.001), and co-immunosuppression with corticosteroids (HR 0.64, P < 0.001) or azathioprine (HR 0.49, P < 0.001) were associated with impaired B-cell repopulation and reconstitution. The effects of corticosteroids (P = 0.043) and azathioprine (P = 0.025) were dose-dependent. Prolonged rituximab dosing intervals may be effective to achieve B-cell depletion and reduce risk of infection in advanced age or patients with impaired kidney function. Co-medication with corticosteroids or azathioprine prolongs B-cell recovery, which may increase therapeutic effects, but also the rate of adverse events.