Circulating complexes between tumour necrosis factor-alpha and etanercept predict long-term efficacy of etanercept in juvenile idiopathic arthritis

Acta Paediatr. 2016 Apr;105(4):427-32. doi: 10.1111/apa.13319. Epub 2016 Feb 1.

Abstract

Aim: The relationship between tumour necrosis factor-alpha (TNF-α) and drug survival had not been studied in juvenile idiopathic arthritis (JIA), and there were no laboratory tests to predict the long-term efficacy of biological drugs for JIA. We studied whether serum levels of TNF-α, free or bound to etanercept, could predict long-term efficacy of etanercept in children with JIA.

Methods: We included 41 biologic-naïve patients with JIA who started treatment with etanercept at Skåne University Hospital between 1999 and 2010. Serum taken at the start of treatment and at the six-week follow-up were analysed for TNF-α and the long-term efficacy of etanercept was assessed using the drug survival time.

Results: Levels of TNF-α increased significantly at the six-week follow-up, and this was almost exclusively comprised of TNF-α in complex with etanercept. The increase in TNF-α showed a dose-dependent correlation to long-term drug survival (p < 0.01).

Conclusion: Increasing levels of circulating TNF-α at treatment initiation predicted long-term efficacy of etanercept in children with JIA, which may have been due to different pathophysiological mechanisms of inflammation. Our result may provide a helpful clinical tool, as high levels of circulating TNF-α/etanercept complexes could be used as a marker for the long-term efficacy of etanercept.

Keywords: Arthritis; Biomarker; Inflammation; Juvenile idiopathic arthritis; Tumour necrosis factor-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antirheumatic Agents / blood*
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Juvenile / blood
  • Arthritis, Juvenile / drug therapy*
  • Child
  • Child, Preschool
  • Etanercept / blood*
  • Etanercept / pharmacology
  • Etanercept / therapeutic use
  • Female
  • Humans
  • Infant
  • Longitudinal Studies
  • Male
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / blood*

Substances

  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Etanercept