Patients non-responding to etanercept obtain lower etanercept concentrations compared with responding patients

Ann Rheum Dis. 2012 Jan;71(1):88-91. doi: 10.1136/annrheumdis-2011-200184. Epub 2011 Sep 12.

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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / blood*
  • Antirheumatic Agents / immunology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy
  • Drug Monitoring / methods
  • Etanercept
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulin G / blood*
  • Immunoglobulin G / immunology
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / administration & dosage*
  • Receptors, Tumor Necrosis Factor / blood*
  • Receptors, Tumor Necrosis Factor / immunology
  • Severity of Illness Index
  • Treatment Failure
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Etanercept