Association of FCGR2A with the response to infliximab treatment of patients with rheumatoid arthritis.

Abstract

OBJECTIVES:

We aimed to assess a functional polymorphism in FCGR2A H131R, for association with the treatment response to Fc-containing inhibitors of tumor necrosis factor (TNF).

METHODS:

A total of 429 biologic-naive patients with rheumatoid arthritis collected in two sets (299 and 130) were treated during standard care with infliximab (INX), etanercept, or adalimumab. Response to the treatment was evaluated at 3, 6, and 12 months of follow-up as the change in the Disease Activity Score (DAS) 28 from baseline and as the response by the European League Against Rheumatism (EULAR) criteria. These variables were analyzed for association with linear and logistic regression models that included sex, inhibitors of TNF, and baseline DAS28 as covariates.

RESULTS:

Significant association was found between the FCGR2A H131R polymorphism and the response to treatment with INX, but not with the other two TNF inhibitors. The 131R allele was associated with a lower change in DAS28 (P=0.04-0.008 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 nonresponders and responders to INX by the EULAR criteria.

CONCLUSION:

We found an association of the FCGR2A 131R allele with poor response to INX. This finding could be of utility to understand the mechanisms behind treatment failure and contribute to biomarker panels for INX response prediction.

• Authors: Ariana Montes, Eva Perez-Pampin, Javier Narváez, Juan D Cañete, Federico Navarro-Sarabia, Virginia Moreira, Antonio Fernández-Nebro, María Del Carmen Ordóñez, Arturo R de la Serna, Berta Magallares, Yiannis Vasilopoulos, Theologia Sarafidou, Rafael Caliz, Miguel Angel Ferrer, Beatriz Joven, Patricia Carreira, Juan J Gómez-Reino, Antonio Gonzalez
• Journal: Pharmacogenetics and genomics (Pharmacogenet Genomics) Vol. 24 Issue 5 Pg. 238-45 (May 2014) ISSN: 1744-6880 [Electronic] United States
• PMID: 24667440 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• FCGR2A protein, human
• Receptors, IgG
• Tumor Necrosis Factor-alpha
• Infliximab
• Adalimumab

Topics

• Adalimumab
• Adult
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Arthritis, Rheumatoid (drug therapy, genetics, pathology)
• Female
• Genetic Association Studies
• Humans
• Infliximab
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Receptors, IgG (genetics)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)