Genetic variants that predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis: current challenges and future directions

Abstract

Tumor necrosis factor alpha (TNF) inhibitors are a mainstay of treatment in rheumatoid arthritis, yet there are no effective clinical or biomarker predictors of which patients will respond. Here we review genetic association studies conducted to search for DNA biomarkers of response to anti-TNF therapy. The entirety of genetic association studies to date that focus on response to anti-TNF therapy has been limited to a small number of genetic variants within a few candidate genes (primarily within the major histocompatibility complex region). Moreover, these studies have been conducted in a relatively small number of rheumatoid arthritis patients (approximately 1000 patients across all studies combined). From these studies, no single genetic factor is associated unequivocally with treatment response, although some studies suggest that alleles within the major histocompatibility complex may influence response. Additional studies are required to investigate the genetic basis of response to anti-TNF therapy. These studies should include an unbiased search of DNA variation across the human genome--now feasible through cost-effective genome-wide association studies--and be conducted in large patient collections powered to detect modest effect sizes.