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Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm‐Van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst‐Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; [...]

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

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  • Media type: E-Article
  • Title: Rheumatoid arthritis risk allele PTPRC is also associated with response to anti–tumor necrosis factor α therapy
  • Contributor: Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm‐Van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst‐Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; [...]
  • imprint: Wiley, 2010
  • Published in: Arthritis & Rheumatism
  • Language: English
  • DOI: 10.1002/art.27457
  • ISSN: 0004-3591; 1529-0131
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Anti–tumor necrosis factor α (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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 (▵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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Of the 31 RA‐associated risk alleles, a SNP at the <jats:italic>PTPRC</jats:italic> (also known as <jats:italic>CD45</jats:italic>) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, <jats:italic>P</jats:italic> = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the ▵DAS28 (<jats:italic>P</jats:italic> = 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).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Statistically significant associations were observed between the response to anti‐TNF therapy and an RA risk allele at the <jats:italic>PTPRC</jats:italic> gene locus. Additional studies will be required to replicate this finding in additional patient collections.</jats:p></jats:sec>
  • Access State: Open Access