title: Double-blind, placebo-controlled randomized trial with adalimumab for treatment of juvenile onset ankylosing spondylitis (JoAS): significant short term improvement.
abstract: BACKGROUND
  While adalimumab is licensed for ankylosing spondylitis (AS), open uncontrolled studies suggest therapeutic efficacy of TNF-inhibitors in juvenile onset AS (JoAS).
  
  
  METHODS
  A total of 32 patients aged 12 to 17 years with severe, active and refractory JoAS were enrolled in a multicenter, randomized, double-blind, placebo-controlled parallel study of 12 weeks, followed by open-label adalimumab until week 24 for all patients. ASAS40 was used as the primary, and ASAS20, PedACR and single items were used as the secondary outcome measures for the intention to treat population.
  
  
  RESULTS
  A total of 17 patients were randomized to receive adalimumab 40 mg/2 weeks and 15 patients received placebo. Two patients (one of each group) discontinued prematurely due to insufficient efficacy and were labeled as non-responders. In the double-blind part, more patients on adalimumab achieved an ASAS40 at week 4 (41%), week 8 (53%) and week 12 (53%) than on placebo (20%, 33%, 33%), while differences at week 8 only reached borderline significance (P = 0.05). Also, at 4, 8 and 12 weeks ASAS20/PedACR30/70 response rates were higher in the adalimumab group (53%/53%/29%; 59%/76%/41%; 53%/65%/53%) compared to placebo (27%/27%/7%; 27%/33%/13%; 33%/40%/27%). In the adalimumab group a significant decrease of all disease activity parameters was noted at week 12 and was even more pronounced at week 24. At week 12 the Bath Ankylosing Spondylitis Disease activity spinal inflammation score decreased by 65% (P <0.001), the back pain score decreased by 50% (P <0.005), the Bath AS Functional Index (BASFI) score decreased by 47% (P <0.02), while the Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) score improved by 65% (P <0.005). ANCOVA analysis demonstrated superiority of adalimumab over placebo for the physician global assessment of disease activity, parents' global assessment of subject's overall well-being, active joint count (all P <0.05) and erythrocyte sedimentation rate (ESR) (P <0.01).
  
  
  CONCLUSIONS
  Adalimumab was well tolerated and highly effective in a double-blind randomized trial in patients with JoAS. Treatment effects rapidly occurred and persisted for at least 24 weeks of treatment.
  
  
  BACKGROUND
  EudraCT 2007-003358-27.
authors.forename: Gerd
authors.initials: G
authors.lastname: Horneff
authors.forename: Sigrid
authors.initials: S
authors.lastname: Fitter
authors.forename: Ivan
authors.initials: I
authors.lastname: Foeldvari
authors.forename: Kirsten
authors.initials: K
authors.lastname: Minden
authors.forename: Jasmin
authors.initials: J
authors.lastname: Kuemmerle-Deschner
authors.forename: Nicolay
authors.initials: N
authors.lastname: Tzaribacev
authors.forename: Angelika
authors.initials: A
authors.lastname: Thon
authors.forename: Michael
authors.initials: M
authors.lastname: Borte
authors.forename: Gerd
authors.initials: G
authors.lastname: Ganser
authors.forename: Rolf
authors.initials: R
authors.lastname: Trauzeddel
authors.forename: Hans-Iko
authors.initials: HI
authors.lastname: Huppertz
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001799:Blood Sedimentation; D002648:Child; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab