title: Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Ankylosing spondylitis is a chronic immune-mediated inflammatory disease characterised by spinal inflammation, progressive spinal rigidity, and peripheral arthritis. Interleukin 17 (IL-17) is thought to be a key inflammatory cytokine in the development of ankylosing spondylitis, the prototypical form of spondyloarthritis. We assessed the efficacy and safety of the anti-IL-17A monoclonal antibody secukinumab in treating patients with active ankylosing spondylitis.
  
  
  METHODS
  We did a randomised double-blind proof-of-concept study at eight centres in Europe (four in Germany, two in the Netherlands, and two in the UK). Patients aged 18-65 years were randomly assigned (in a 4:1 ratio) to either intravenous secukinumab (2×10 mg/kg) or placebo, given 3 weeks apart. Randomisation was done with a computer-generated block randomisation list without a stratification process. The primary efficacy endpoint was the percentage of patients with a 20% response according to the Assessment of SpondyloArthritis international Society criteria for improvement (ASAS20) at week 6 (Bayesian analysis). Safety was assessed up to week 28. This study is registered with ClinicalTrials.gov, number NCT00809159.
  
  
  RESULTS
  37 patients with moderate-to-severe ankylosing spondylitis were screened, and 30 were randomly assigned to receive either intravenous secukinumab (n=24) or placebo (n=6). The final efficacy analysis included 23 patients receiving secukinumab and six patients receiving placebo, and the safety analysis included all 30 patients. At week 6, ASAS20 response estimates were 59% on secukinumab versus 24% on placebo (99·8% probability that secukinumab is superior to placebo). One serious adverse event (subcutaneous abscess caused by Staphylococcus aureus) occurred in the secukinumab-treated group.
  
  
  CONCLUSIONS
  Secukinumab rapidly reduced clinical or biological signs of active ankylosing spondylitis and was well tolerated. It is the first targeted therapy that we know of that is an alternative to tumour necrosis factor inhibition to reach its primary endpoint in a phase 2 trial.
  
  
  BACKGROUND
  Novartis.
authors.affiliation: Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
authors.forename: Xenofon
authors.initials: X
authors.lastname: Baraliakos
authors.forename: Jürgen
authors.initials: J
authors.lastname: Braun
authors.forename: Joachim
authors.initials: J
authors.lastname: Sieper
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
authors.forename: Iain
authors.initials: I
authors.lastname: McInnes
authors.forename: Jacob M
authors.initials: JM
authors.lastname: van Laar
authors.forename: Robert
authors.initials: R
authors.lastname: Landewé
authors.forename: Paul
authors.initials: P
authors.lastname: Wordsworth
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wollenhaupt
authors.forename: Herbert
authors.initials: H
authors.lastname: Kellner
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Paramarta
authors.forename: Jiawei
authors.initials: J
authors.lastname: Wei
authors.forename: Arndt
authors.initials: A
authors.lastname: Brachat
authors.forename: Stephan
authors.initials: S
authors.lastname: Bek
authors.forename: Didier
authors.initials: D
authors.lastname: Laurent
authors.forename: Yali
authors.initials: Y
authors.lastname: Li
authors.forename: Ying A
authors.initials: YA
authors.lastname: Wang
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Bertolino
authors.forename: Sandro
authors.initials: S
authors.lastname: Gsteiger
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Wright
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hueber
mesh_terms: D000038:Abscess / Q000139:chemically induced; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000150:complications / Q000188:drug therapy*; D013207:Staphylococcal Skin Infections / Q000139:chemically induced; D013211:Staphylococcus aureus; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; C555450:secukinumab