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Rheumatoid Arthritis Risk Allele PTPRC Is Also Associated With Response to Anti-Tumor Necrosis Factor alpha Therapy

Lookup NU author(s): Professor John IsaacsORCiD


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Objective. Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. Methods. A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (Delta DAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. Results. Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the Delta DAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39-0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41-1.99). Conclusion. Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections.

Publication metadata

Author(s): Cui J, Saevarsdottir S, Thomson B, Padyukov L, van der Helm-van Mil AHM, Nititham J, Hughes LB, de Vries N, Raychaudhuri S, Alfredsson L, Askling J, Wedren S, Ding B, Guiducci C, Wolbink GJ, Crusius JBA, van der Horst-Bruinsma IE, Herenius M, Weinblatt ME, Shadick NA, Worthington J, Batliwalla F, Kern M, Morgan AW, Wilson AG, Isaacs JD, Hyrich K, Seldin MF, Moreland LW, Behrens TW, Allaart CF, Criswell LA, Huizinga TWJ, Tak PP, Bridges SL, Toes REM, Barton A, Klareskog L, Gregersen PK, Karlson EW, Plenge RM, Biol Rheumatoid Arthrit Genet & Ge

Publication type: Article

Publication status: Published

Journal: Arthritis & Rheumatism

Year: 2010

Volume: 62

Issue: 7

Pages: 1849-1861

Print publication date: 22/03/2010

ISSN (print): 0004-3591

ISSN (electronic): 1529-0131

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/art.27457


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Funder referenceFunder name
American College of Rheumatology Research and Education Foundation
European Community
Harvard University
Stockholm County Council
Swedish COMBINE project
Biogen Idec
Bristol-Myers Squibb
Burroughs Wellcome Fund
Crescendo Bioscience
Flight Attendant Medical Research Institute
Swedish Council for Working Life and Social Research, King Gustaf V's 80-Year Foundation
Swedish Medical Research Council
Swedish Rheumatism Association
945-02-029Netherlands Organisation for Health Research and Development (ZonMw)
R01-AR-056768NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases)
R01-AR-057108NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases)