title: Circulating complexes between tumour necrosis factor-alpha and etanercept predict long-term efficacy of etanercept in juvenile idiopathic arthritis.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Robin
authors.initials: R
authors.lastname: Kahn
authors.affiliation: Department of Rheumatology, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Berthold
authors.affiliation: Department of Rheumatology, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Gullstrand
authors.affiliation: Department of Pediatrics, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmidt
authors.affiliation: Department of Infection Medicine, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Kahn
authors.affiliation: Department of Rheumatology, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Pierre
authors.initials: P
authors.lastname: Geborek
authors.affiliation: Department of Rheumatology, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Tore
authors.initials: T
authors.lastname: Saxne
authors.affiliation: Department of Rheumatology, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Anders A
authors.initials: AA
authors.lastname: Bengtsson
authors.affiliation: Department of Rheumatology, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Månsson
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000097:blood / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D000068800:Etanercept / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept
keywords: Arthritis; Biomarker; Inflammation; Juvenile idiopathic arthritis; Tumour necrosis factor-alpha