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

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.