title: Patients non-responding to etanercept obtain lower etanercept concentrations compared with responding patients.
abstract: OBJECTIVE
  To investigate the relationship between serum etanercept levels and clinical response.
  
  
  METHODS
  In 292 etanercept-treated patients with rheumatoid arthritis clinical and pharmacological data were determined at baseline and after 1, 4 and 6 months of etanercept treatment. Differences in etanercept levels between good, moderate and European League Against Rheumatism (EULAR) non-responders were assessed after 6 months of therapy.
  
  
  RESULTS
  After 6 months of therapy etanercept levels were significantly higher in good responders (median (IQR) 3.78 (2.53-5.17)) compared with both moderate 3.10 (2.12-4.47) and EULAR non-responders 2.80 (1.27-3.93) (all p<0.05). There was a significant association between clinical response and serum etanercept levels (regression coefficient 0.54, 95% CI 0.21 to 0.86, p=0.001). When patients were categorised into quartiles according to the height of etanercept levels, the lowest quartile (etanercept level <2.1 mg/l) comprised 40% of all non-responders. The highest quartile (etanercept level >4.7 mg/l) comprised 35% of all good EULAR responders. Anti-etanercept antibodies were detected in none of the sera.
  
  
  CONCLUSIONS
  The authors demonstrated that lower etanercept levels were associated with non-response. Therapeutic drug monitoring and the possibility of the adjusted dosing regimes in the selected groups of patients should be investigated further as a possible tool to optimise treatment with etanercept.
authors.affiliation: Jan van Breemen Research Institute/Reade, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Jamnitski
authors.forename: C L
authors.initials: CL
authors.lastname: Krieckaert
authors.forename: M T
authors.initials: MT
authors.lastname: Nurmohamed
authors.forename: M H
authors.initials: MH
authors.lastname: Hart
authors.forename: B A
authors.initials: BA
authors.lastname: Dijkmans
authors.forename: L
authors.initials: L
authors.lastname: Aarden
authors.forename: A E
authors.initials: AE
authors.lastname: Voskuyl
authors.forename: G J
authors.initials: GJ
authors.lastname: Wolbink
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy; D016903:Drug Monitoring / Q000379:methods; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage* / Q000097:blood* / Q000276:immunology; D012720:Severity of Illness Index; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept