The effect of gene polymorphisms on patient responses to rheumatoid arthritis therapy

Abstract

Introduction: Rheumatoid arthritis (RA) is a systemic disease leading to joint destruction. The therapy of RA is mainly based on disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs. The response to treatment is different among patients. Therefore, we have searched for factors that may predict the efficacy and toxicity during therapy in individual patients.Areas covered: This review presents the role of genetic polymorphisms as predictors of the efficacy and toxicity during the therapy of RA patients with DMARDs (methotrexate, leflunomide, sulfasalazine) and biological drugs (anti-TNF-alpha antagonists, Tocilizumab, Rituximab).Expert opinion: Despite studies having shown an association between genetic polymorphisms and response to therapy in RA patients, the majority of these findings are still inconclusive and inconsistent. We are still far from applying pharmacogenetic tests in routine clinical practice that can predict the outcome of treatment. Several factors, such as small sample size with low statistical power, variability in the outcome definitions and the heterogeneity of the cohorts, limited number of tested single nucleotide polymorphisms (SNPs), small effect for the selected variant, and a lack of consideration of epigenetic factors, may contribute to the inconsistency observed and may lead to limited success in personalizing therapy.