title: Lower etanercept levels are associated with high disease activity in ankylosing spondylitis patients at 24 weeks of follow-up.
abstract: BACKGROUND
  Previous data have shown that etanercept levels are associated with clinical response in rheumatoid arthritis. However, for ankylosing spondylitis (AS), data regarding this topic are inconclusive.
  
  
  OBJECTIVE
  To investigate the relationship between etanercept levels and clinical response in patients with AS.
  
  
  METHODS
  Observational prospective cohort study of 162 patients with AS =treated with etanercept, monitored during 24 weeks of treatment. Etanercept trough levels were determined, retrospectively, using an ELISA. Disease activity was measured using AS Disease Activity Score (ASDAS), including C-reactive protein (CRP) and Bath AS Disease Activity index (BASDAI). Active disease was defined as ASDAS≥2.1. Since etanercept is a drug administered at home there might have been some variation in trough level sampling.
  
  
  RESULTS
  At 24 weeks etanercept levels were significantly higher in patients with ASDAS<2.1, (3.8 mg/L; IQR 2.5-5.2) compared with patients with ASDAS≥2.1 (2.3 mg/L; IQR 1.2-3.4; p≤0.001). Generalised estimating equation analysis demonstrated a statistically significant association between etanercept levels and ASDAS, BASDAI, CRP and erythrocyte sedimentation rate (all p<0.001). When patients were categorised into quartiles according to etanercept levels, the lowest quartile (etanercept<1.80 mg/L) comprised 35% of all patients with ASDAS≥2.1 while the highest quartile comprised only 14%.
  
  
  CONCLUSIONS
  Disease activity and inflammation are associated with etanercept levels in patients with AS at 24 weeks of treatment. Measuring etanercept levels might help in identifying overtreatment and undertreatment and optimise etanercept therapy in AS.
authors.affiliation: Department of Rheumatology, Jan van Breemen Research Institute|Reade, Amsterdam, The Netherlands.
authors.forename: E L
authors.initials: EL
authors.lastname: Kneepkens
authors.affiliation: Department of Rheumatology, Jan van Breemen Research Institute|Reade, Amsterdam, The Netherlands.
authors.forename: C L M
authors.initials: CL
authors.lastname: Krieckaert
authors.affiliation: Laboratory for Monoclonal Therapeutics, Sanquin Diagnostic Services, Amsterdam, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: van der Kleij
authors.affiliation: Department of Rheumatology, Jan van Breemen Research Institute|Reade, Amsterdam, The Netherlands Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: M T
authors.initials: MT
authors.lastname: Nurmohamed
authors.affiliation: Department of Rheumatology, Jan van Breemen Research Institute|Reade, Amsterdam, The Netherlands Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: I E
authors.initials: IE
authors.lastname: van der Horst-Bruinsma
authors.affiliation: Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Rispens
authors.affiliation: Department of Rheumatology, Jan van Breemen Research Institute|Reade, Amsterdam, The Netherlands Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Wolbink
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000097:blood* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods; D000068800:Etanercept / Q000097:blood* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts / Q000706:statistics & numerical data; D011446:Prospective Studies; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood* / Q000188:drug therapy
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D002097:C-Reactive Protein; D000068800:Etanercept
keywords: Ankylosing Spondylitis; Anti-TNF; Pharmacokinetics; TNF-alpha; Treatment