Abstract
Objective. 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. 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 (ΔDAS28). 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 ΔDAS28 (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 language | English (US) |
|---|---|
| Pages (from-to) | 1849-1861 |
| Number of pages | 13 |
| Journal | Arthritis and Rheumatism |
| Volume | 62 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2010 |
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ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Rheumatology
- Pharmacology (medical)
Cite this
Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor α therapy. / 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.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W J; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E M; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.
In: Arthritis and Rheumatism, Vol. 62, No. 7, 07.2010, p. 1849-1861.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor α therapy
AU - Cui, Jing
AU - Saevarsdottir, Saedis
AU - Thomson, Brian
AU - Padyukov, Leonid
AU - Van Der Helm-van Mil, Annette H M
AU - Nititham, Joanne
AU - Hughes, Laura B.
AU - De Vries, Niek
AU - Raychaudhuri, Soumya
AU - Alfredsson, Lars
AU - Askling, Johan
AU - Wedrén, Sara
AU - Ding, Bo
AU - Guiducci, Candace
AU - Wolbink, Gert Jan
AU - Crusius, J. Bart A
AU - Van Der Horst-Bruinsma, Irene E.
AU - Herenius, Marieke
AU - Weinblatt, Michael E.
AU - Shadick, Nancy A.
AU - Worthington, Jane
AU - Batliwalla, Franak
AU - Kern, Marlena
AU - Morgan, Ann W.
AU - Wilson, Anthony G.
AU - Isaacs, John D.
AU - Hyrich, Kimme
AU - Seldin, Michael F
AU - Moreland, Larry W.
AU - Behrens, Timothy W.
AU - Allaart, Cornelia F.
AU - Criswell, Lindsey A.
AU - Huizinga, Tom W J
AU - Tak, Paul P.
AU - Bridges, S. Louis
AU - Toes, Rene E M
AU - Barton, Anne
AU - Klareskog, Lars
AU - Gregersen, Peter K.
AU - Karlson, Elizabeth W.
AU - Plenge, Robert M.
PY - 2010/7
Y1 - 2010/7
N2 - Objective. 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. 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 (ΔDAS28). 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 ΔDAS28 (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.
AB - Objective. 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. 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 (ΔDAS28). 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 ΔDAS28 (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.
UR - http://www.scopus.com/inward/record.url?scp=77954241353&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954241353&partnerID=8YFLogxK
U2 - 10.1002/art.27457
DO - 10.1002/art.27457
M3 - Article
C2 - 20309874
AN - SCOPUS:77954241353
VL - 62
SP - 1849
EP - 1861
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
SN - 2326-5191
IS - 7
ER -