Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy

Jing Cui, Saedis Saevarsdottir, Brian Thomson, Leonid Padyukov, Annette H. M. van der Helm-van Mil, Joanne Nititham, Laura B. Hughes, Niek de Vries, Soumya Raychaudhuri, Lars Alfredsson, Johan Askling, Sara Wedrén, Bo Ding, Candace Guiducci, Gert Jan Wolbink, J. Bart A. Crusius, Irene E. van der Horst-Bruinsma, Marieke Herenius, Michael E. Weinblatt, Nancy A. ShadickJane Worthington, Franak Batliwalla, Marlena Kern, Ann W. Morgan, Anthony G. Wilson, John D. Isaacs, Kimme Hyrich, Michael F. Seldin, Larry W. Moreland, Timothy W. Behrens, Cornelia F. Allaart, Lindsey A. Criswell, Tom W. J. Huizinga, Paul P. Tak, S. Louis Bridges, Rene E. M. Toes, Anne Barton, Lars Klareskog, Peter K. Gregersen, Elizabeth W. Karlson, Robert M. Plenge

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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 (triangle upDAS28). 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 triangle upDAS28 (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
Original languageEnglish
Pages (from-to)1849-1861
JournalArthritis and rheumatism
Issue number7
Publication statusPublished - 2010

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