Association of FCGR2A with the response to infliximab treatment of patients with rheumatoid arthritis.
Montes Martínez, Ariadna; Pérez Pampín, Eva; Narváez, Javier; Cañete, Juan D; Navarro-Sarabia, Federico; Moreira, Virginia; Fernández Nebro, Antonio; Ordóñez, María del Carmen; De la Serna, Arturo R; Magallares, Berta; Vasilopoulos, Yiannis; Sarafidou, Theologia; Caliz, Rafael; Ferrer, Miguel Angel; Joven, Beatriz; Carreira, Patricia; Gómez-Reino Carnota, Juan Jesús; González Martínez-Pedrayo, Antonio
Identifiers
Identifiers
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Date issued
2014-05Journal title
Pharmacogenetics and Genomics
Type of content
Artigo
DeCS
receptores de IgG | anticuerpos monoclonales | estudios de asociación genética | factor de necrosis tumoral alfa | reumatología | artritis reumatoide | artritisMeSH
Tumor Necrosis Factor-alpha | Arthritis, Rheumatoid | Receptors, IgG | Genetic Association Studies | Rheumatology | Infliximab | Antibodies, Monoclonal | Etanercept | Spain | Arthritis | AdalimumabAbstract
[EN] Objectives: We aimed to assess a functional polymorphism in FCGR2A, H131R, for association with treatment response to Fc-containing inhibitors of TNF. Methods: A total of 429 biologic-naïve patients with rheumatoid arthritis (RA) collected in two sets (299 and 130) were treated during standard care with Infliximab, Etanercept or Adalimumab. Response to treatment was evaluated at 3, 6 and 12 months of follow-up as change in Disease Activity Score (DAS) 28 from baseline and as response by the European League Against Rheumatism (EULAR) criteria. These variables were analyzed for association with linear and logistic regression models that included gender, inhibitor of TNF and baseline DAS28 as covariates. Results: Significant association was found between the FCGR2A H131R polymorphism and response to treatment with Infliximab, but not with the other two TNF inhibitors. The 131R allele was associated with a lower change in DAS28 (P = 0.04 to 0.008 at different times) in the first set of patients and confirmed in the second group of patients (P = 0.026 at 3 months of follow-up). Association was also found in the comparison between non-responders and responders to Infliximab by the EULAR criteria. Conclusions: We have found association of the FCGR2A 131R allele with poor response to Infliximab. This finding could be of utility to understand the mechanisms behind treatment failure and contribute to biomarker panels for Infliximab response prediction.