Pharmacogenetics of etanercept: role of TNF-α gene polymorphisms in improving its efficacy

Introduction: During the last decade, many new biological immune modulators have entered the market as new therapeutic principles. Biologics, including TNF-alpha inhibitors, are the new frontier in the treatment of immune-mediated or inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, ankylosing spondylitis, systemic sclerosis, disseminated granuloma annulare, psoriasis and/or psoriatic arthritis. TNF-alpha inhibitors have demonstrated efficacy and are well tolerated in large, randomized,controlled clinical trials. However, a substantial proportion of patients do not respond to these agents and potential adverse drug reactions may be associated with its use. Areas covered: Pharmacogenetics has the potential of increasing drug efficiency by identifying genetic factors responsible for lack of response or toxicities to TNF-alpha inhibitors. In this review, we analyze the influence of several polymorphisms upon the efficacy and safety of TNF-alpha inhibitors. Expert opinion: Several polymorphisms have been proven to influence the response to etanercept. Among them, single nucleotide polymorphisms (SNPs) -308 G/G, -857 C/T, +489 GG and GA, HLA-DRB1-encoding SE (allele *0404 and allele *0101) favor the response to etanercept, whereas SNP -308 A/A and TNFR1A AA decrease the response. Large clinical studies are needed to confirm the relevance of these associations in order to tailor treatment and to decrease unnecessary toxicity.