TRAF1/C5 but not PTPRC variants are potential predictors of rheumatoid arthritis response to anti-tumor necrosis factor therapy.

Helena Canhão,Ileana Filipescu,Rafael Cáliz,Robert M Plenge,Jácome Bruges-Armas,Daniel H Solomon,Jaime Branco,Joaquim Polido-Pereira,João Eurico Fonseca,Helena Santos,Cândida Silva,Cátia Duarte,Jing Cui,Fernando Pimentel-Santos,Diana Carmona-Fernandes,Maria José Santos,Juan Sainz,José Alberto Pereira Silva,Elizabeth W Karlson,José António Costa,José António Pereira Da Silva ,Domingos Araújo ,José Canas Da Silva ,Fabiana Lucena Rocha ,Bruno Filipe Bettencourt

doi:10.1155/2015/490295

Abstract

Background. The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response. Methods. We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients. Results. No association was found between PTPRC rs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis. Conclusion. This study did not replicate the association between PTPRC and the response to anti-TNF treatment in our Southern European population. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response.

Highlights

Rheumatoid arthritis (RA) is an inflammatory, chronic, and disabling disease
119 (31.1%) patients were classified as good responders, 175 (45.7%) as moderate responders, and 89 (23.2%) as nonresponders according to the EULAR response criteria [37]
Number of years completed at school, Health Assessment Questionnaire (HAQ), and DAS28 at baseline were found to have a significant association with treatment response at six months and were included in the multivariate models (Table 2)

Summary

Introduction

Rheumatoid arthritis (RA) is an inflammatory, chronic, and disabling disease. Methotrexate is the most widely used disease modifying antirheumatic drug (DMARD) in RA treatment. For refractory and severe cases, antitumor necrosis factor (anti-TNF) therapy has become a cornerstone of RA treatment strategy [1]. These drugs have revolutionized RA treatment and prognosis in the last 10–15 years. The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). No association was found between PTPRC rs10919563 allele and antiTNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response

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Discussion

Conclusion