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

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Abstract

OBJECTIVE:: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of our study is to test established RA genetic risk factors to determine if the same alleles also influence response to anti-TNF therapy. METHODS:: A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were drawn from an international collaboration consisting of 9 different RA cohorts. The primary endpoint compared EULAR 'good response' RA patients (n=505) to 'no response' patients (n=316); the secondary endpoint used change in Disease Activity Score (DAS28) from baseline ('delta-DAS28'). We tested clinical factors such as age, sex, and concomitant medications as correlates of treatment response. We genotyped 31 single nucleotide polymorphisms (SNPs) associated with risk of RA, and tested for 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 was associated with the primary endpoint, EULAR 'good response' vs 'no response' (rs10919563, OR=0.55, P=0.0001 in a multivariate model). Similar results were obtained using the secondary endpoint (P=0.0002). We found suggestive evidence of a stronger association in autoantibody positive (OR=0.55 95% CI 0.39-0.76) compared to autoantibody negative patients (OR=0.90 95% CI 0.41-1.99). CONCLUSION:: We observed statistically significant associations between 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.

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