title: Pharmacogenetics of etanercept: role of TNF-α gene polymorphisms in improving its efficacy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Genova, Department of Internal Medicine, Clinical Immunology Unit , Viale Benedetto XV, n. 6 16132 Genova , Italy +39 010 353 7924 ; +39 010 555 6950 ; Giuseppe.Murdaca@unige.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Murdaca
authors.forename: Francesca
authors.initials: F
authors.lastname: Spanò
authors.forename: Miriam
authors.initials: M
authors.lastname: Contatore
authors.forename: Andrea
authors.initials: A
authors.lastname: Guastalla
authors.forename: Ottavia
authors.initials: O
authors.lastname: Magnani
authors.forename: Francesco
authors.initials: F
authors.lastname: Puppo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D018579:Patient Selection; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics*
chemical_list: D000893:Anti-Inflammatory Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept
keywords: TNF-α gene polymorphisms; TNF-α inhibitors; etanercept; immune-mediated diseases