title: Symptomatic efficacy of etanercept and its effects on objective signs of inflammation in early nonradiographic axial spondyloarthritis: a multicenter, randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  To assess the efficacy of etanercept in the treatment of early active nonsteroidal antiinflammatory drug (NSAID)-refractory nonradiographic axial spondyloarthritis (SpA).
  
  
  METHODS
  The study population consisted of patients who met the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA but not the modified New York radiographic criteria for ankylosing spondylitis (as assessed by a radiologist at the central trial site), had a symptom duration of >3 months but <5 years, had a score of ≥4 on the Bath Ankylosing Spondylitis Disease Activity Index, and had been treated unsuccessfully with ≥2 NSAIDs. Patients were randomized to receive etanercept 50 mg/week or placebo and continued background NSAID treatment for 12 weeks (double-blind study); during the subsequent open-label period, all patients received etanercept 50 mg/week. The primary study end point was meeting the ASAS criteria for 40% improvement (ASAS40) at week 12. Magnetic resonance imaging (MRI) of the sacroiliac joints and spine was performed at baseline and week 12.
  
  
  RESULTS
  One hundred six patients were randomized to the etanercept group and 109 to the placebo group. Of the 215 patients, the mean ± SD age at baseline was 32.0 ± 7.8 years, 154 (72%) were HLA-B27 positive, and 174 (81%) had MRI-confirmed sacroiliitis. At 12 weeks, the proportion of patients with improvement according to the ASAS40 was significantly higher in the etanercept group than in the placebo group (34 of 105 [32%] versus 17 of 108 [16%]; P = 0.006). Patients who received etanercept exhibited a greater reduction in MRI-based scores for sacroiliac joint inflammation (-46.9% versus -10.9%; P < 0.001) and spinal inflammation (-45.4% versus -33.4%; P = 0.04) compared with placebo-treated patients at week 12. Post hoc analyses suggested a possible association between higher baseline C-reactive protein levels or MRI sacroiliac joint inflammation scores and higher rates of ASAS40 response to etanercept. At week 24, patients in the placebo group who had switched to etanercept at 12 weeks exhibited improvement similar to that observed in patients who had received etanercept for 24 weeks.
  
  
  CONCLUSIONS
  In patients with nonradiographic axial SpA, etanercept treatment was associated with rapid, significant improvement in symptomatic disease activity, function, and systemic and skeletal inflammation over 12 weeks; clinical/functional improvement was sustained over 24 weeks.
authors.affiliation: Université Pierre et Marie Curie Paris 6, Hôpital Cochin, AP-HP, INSERM U1153, and PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
authors.forename: Joachim
authors.initials: J
authors.lastname: Sieper
authors.forename: Jürgen
authors.initials: J
authors.lastname: Braun
authors.forename: Walter P
authors.initials: WP
authors.lastname: Maksymowych
authors.forename: Gustavo
authors.initials: G
authors.lastname: Citera
authors.forename: Corinne
authors.initials: C
authors.lastname: Miceli-Richard
authors.forename: James Cheng-Chung
authors.initials: JC
authors.lastname: Wei
authors.forename: Ron
authors.initials: R
authors.lastname: Pedersen
authors.forename: Randi
authors.initials: R
authors.lastname: Bonin
authors.forename: Mahboob U
authors.initials: MU
authors.lastname: Rahman
authors.forename: Isabelle
authors.initials: I
authors.lastname: Logeart
authors.forename: Joseph
authors.initials: J
authors.lastname: Wajdula
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Koenig
authors.forename: Bonnie
authors.initials: B
authors.lastname: Vlahos
authors.forename: Daniel
authors.initials: D
authors.lastname: Alvarez
authors.forename: Jack F
authors.initials: JF
authors.lastname: Bukowski
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012074:Remission Induction; D025241:Spondylarthritis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept