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

Research output: Contribution to journalArticle

87 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1849-1861
Number of pages13
JournalArthritis and Rheumatism
Volume62
Issue number7
DOIs
StatePublished - Jul 2010

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Rheumatoid Arthritis
Tumor Necrosis Factor-alpha
Alleles
Therapeutics
Odds Ratio
Autoantibodies
Single Nucleotide Polymorphism
Joints
Logistic Models
Confidence Intervals
Rheumatic Diseases
Genes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Cui, J., Saevarsdottir, S., Thomson, B., Padyukov, L., Van Der Helm-van Mil, A. H. M., Nititham, J., ... Plenge, R. M. (2010). Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor α therapy. Arthritis and Rheumatism, 62(7), 1849-1861. https://doi.org/10.1002/art.27457

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 journalArticle

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, Wedrén, 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 2010, 'Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor α therapy', Arthritis and Rheumatism, vol. 62, no. 7, pp. 1849-1861. https://doi.org/10.1002/art.27457
Cui J, Saevarsdottir S, Thomson B, Padyukov L, Van Der Helm-van Mil AHM, Nititham J et al. Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor α therapy. Arthritis and Rheumatism. 2010 Jul;62(7):1849-1861. https://doi.org/10.1002/art.27457
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. / Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor α therapy. In: Arthritis and Rheumatism. 2010 ; Vol. 62, No. 7. pp. 1849-1861.
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title = "Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor α therapy",
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.",
author = "Jing Cui and Saedis Saevarsdottir and Brian Thomson and Leonid Padyukov and {Van Der Helm-van Mil}, {Annette H M} and Joanne Nititham and Hughes, {Laura B.} and {De Vries}, Niek and Soumya Raychaudhuri and Lars Alfredsson and Johan Askling and Sara Wedr{\'e}n and Bo Ding and Candace Guiducci and Wolbink, {Gert Jan} and Crusius, {J. Bart A} and {Van Der Horst-Bruinsma}, {Irene E.} and Marieke Herenius and Weinblatt, {Michael E.} and Shadick, {Nancy A.} and Jane Worthington and Franak Batliwalla and Marlena Kern and Morgan, {Ann W.} and Wilson, {Anthony G.} and Isaacs, {John D.} and Kimme Hyrich and Seldin, {Michael F} and Moreland, {Larry W.} and Behrens, {Timothy W.} and Allaart, {Cornelia F.} and Criswell, {Lindsey A.} and Huizinga, {Tom W J} and Tak, {Paul P.} and Bridges, {S. Louis} and Toes, {Rene E M} and Anne Barton and Lars Klareskog and Gregersen, {Peter K.} and Karlson, {Elizabeth W.} and Plenge, {Robert M.}",
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language = "English (US)",
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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.

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