Pharmacogenetics of anti-TNF treatment in patients with rheumatoid arthritis.
TNF-blocking strategies are widely used in the treatment of rheumatoid arthritis (RA). Three anti-TNF agents are registered for use in RA: etanercept, infliximab and adalimumab. Although anti-TNF therapy is very effective in controlling disease activity and slowing down radiological damage, prolonged response is only seen in approximately 70% of the patients. The causes for nonresponse in the remaining patients have not yet been elucidated. Pharmacogenetic studies focusing on genes involved in RA etiology (and/or progression) and in the pharmacokinetics of TNF-blocking agents have identified markers associated with anti-TNF treatment outcome. In the future, more exhaustive, less hypothesis-driven search strategies are expected to discover additional markers. Identification of these markers might be viewed as the first step towards tailored TNF-blocking therapy for patients with RA. Nevertheless, replication and large prospective studies will be needed to demonstrate the validity of the identified genetic markers before implementation into daily clinical practice.
Coenen
Marieke J H
MJ
Radboud University, Nijmegen Medical Centre, Department of Human Genetics, Internal Mail 855, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. m.coenen@antrg.umcn.nl
Toonen
Erik J M
EJ
Scheffer
Hans
H
Radstake
Timothy R D J
TR
Barrera
Pilar
P
Franke
Barbara
B
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D015331:Cohort Studies; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D018579:Patient Selection; D010597:Pharmacogenetics / Q000379:methods; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept