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

Giuseppe Murdaca, Francesca Spanò, Miriam Contatore, Andrea Guastalla, Ottavia Magnani, Francesco Puppo

Research output: Contribution to journalArticlepeer-review


Introduction: During the last decade, many new biological immune modulators have entered the market as new therapeutic principles. Biologics, including TNF-α 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-α 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-α inhibitors. In this review, we analyze the influence of several polymorphisms upon the efficacy and safety of TNF-α 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.

Original languageEnglish
Pages (from-to)1703-1710
Number of pages8
JournalExpert Opinion on Drug Metabolism and Toxicology
Issue number12
Publication statusPublished - Dec 1 2014


  • Etanercept
  • Immune-mediated diseases
  • TNF-α gene polymorphisms
  • TNF-α inhibitors

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Medicine(all)


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