title: Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN).
abstract: OBJECTIVE
  The ALIGN study (NCT01061723) evaluated the efficacy and safety of sarilumab, the first fully human monoclonal antibody against interleukin-6 receptor-α (IL-6Rα), in patients with ankylosing spondylitis (AS).
  
  
  METHODS
  Patients with active AS despite conventional treatment were randomised to placebo, or one of five subcutaneous dose regimens of sarilumab (100, 150 or 200 mg every other week, or 100 or 150 mg every week), for 12 weeks. The primary efficacy end point was the percentage of patients achieving the Axial SpondyloArthritis international Society (ASAS) 20 response criteria at week 12. Secondary endpoints included ASAS40 response, ASAS partial remission, AS Disease Activity Score, high-sensitivity C-reactive protein (hs-CRP) value, and safety.
  
  
  RESULTS
  Baseline demographic and disease characteristics of the 301 patients enrolled were similar across treatment groups. At week 12, there was no statistically significant difference in ASAS20 response rate between placebo (ASAS20 = 24.0%) and any sarilumab dose group. A significantly greater reduction in hs-CRP value was achieved with the higher sarilumab doses versus placebo. No other statistically significant differences were evident for secondary efficacy endpoints. The most common treatment-emergent adverse events reported for sarilumab included infections (non-serious), neutropenia, and increase in alanine aminotransferase. No cases of tuberculosis, opportunistic, or fungal infections, or bowel perforations were reported. Seven patients experienced a treatment-emergent serious adverse event (all in sarilumab treatment groups). No deaths occurred.
  
  
  CONCLUSIONS
  The ALIGN study shows that IL-6Rα blockade with sarilumab was not an effective treatment for AS. Sarilumab was generally well tolerated with a manageable safety profile.
authors.affiliation: Med. Department 1, Rheumatology, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Sieper
authors.affiliation: Rheumazentrum Ruhrgebiet, Herne, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Braun
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kay
authors.affiliation: Research and Development, Sanofi, Bridgewater, New Jersey, USA.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Badalamenti
authors.affiliation: Translational Medicine, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
authors.forename: Allen R
authors.initials: AR
authors.lastname: Radin
authors.affiliation: Research and Development, Sanofi, Bridgewater, New Jersey, USA.
authors.forename: Lixia
authors.initials: L
authors.lastname: Jiao
authors.affiliation: Research and Development, Sanofi, Bridgewater, New Jersey, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiore
authors.affiliation: Research and Development, Sanofi, Bridgewater, New Jersey, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Momtahen
authors.affiliation: Translational Medicine, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.affiliation: Translational Medicine, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Stahl
authors.affiliation: Division of Rheumatology, Toronto Hospital Western Division, Toronto, Canada.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Inman
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors; D012074:Remission Induction; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D019947:Receptors, Interleukin-6; C113250:interleukin-6 receptor alpha; D002097:C-Reactive Protein; C000592401:sarilumab
keywords: Ankylosing Spondylitis; Autoimmune Diseases; Cytokines; DMARDs (biologic); Inflammation