Identification of Covariates Modulating B‐Cell Repopulation Kinetics in Subjects Receiving Rituximab Treatment.
Objective: 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 time span of B‐cell repopulation differs greatly between individ...
| Published in: | Arthritis & Rheumatology Vol. 75; no. 11; pp. 2045 - 2054 |
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| Main Authors: | , , , , , , , , |
| Format: | research tables/charts Journal Article |
| Published: |
Wiley-Blackwell
Nov2023
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=173312728&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 173312728 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23265191 H06R jtl: Arthritis & Rheumatology issn: 23265191 maglogo: N pubinfo: dt: Nov2023 vid: 75 iid: 11 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 173312728 171563441 173312728 173312728 10.1002/art.42625 173312728 ppf: 2045 ppct: 9 formats: tig: atl: Identification of Covariates Modulating B‐Cell Repopulation Kinetics in Subjects Receiving Rituximab Treatment. aug: au: Welte, Thomas Westermann, Lukas Kappes, Julia Schramm, Markus A. Bemtgen, Xavier Staudacher, Dawid L. Hug, Martin J. Venhoff, Nils Arnold, Frederic affil: Department of Medicine IV, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany sug: subj: Adrenal Cortex Hormones Therapeutic Use Kidney Diseases Therapy Vasculitis Complications Azathioprine Therapeutic Use Cyclophosphamide Therapeutic Use Immunosuppressive Agents Therapeutic Use Rituximab Therapeutic Use B Lymphocytes Immunology Infection Prevention and Control Human Descriptive Statistics Male Female Adult Middle Age Confidence Intervals Comparative Studies Retrospective Design Observational Methods Adult: 19-44 years Middle Aged: 45-64 years Male Female ab: Objective: 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 time span 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. Methods: This single‐center retrospective observational study presents data of 839 subjects receiving 2,017 courses of rituximab for autoimmune diseases. 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 end point is the time to B‐cell repopulation (≥5/μl). The secondary end point is the time to B‐cell reconstitution (≥50/μl). Multivariate time‐to‐event analysis and logistic regression models were applied to estimate the influence of covariates. Results: Age over 60 years (hazard ratio [HR] 0.71 for repopulation, P = 0.008), impaired kidney function (HR 0.72, P = 0.001), antineutrophil cytoplasmic antibody‐associated vasculitis (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. Effects of corticosteroids (P = 0.043) and azathioprine (P = 0.025) were dose dependent. Conclusion: 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. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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