title: Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study.
abstract: OBJECTIVE
  To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis).
  
  
  METHODS
  In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored.
  
  
  RESULTS
  Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; p<0.001); tofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16.
  
  
  CONCLUSIONS
  Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications.
  
  
  BACKGROUND
  NCT01786668.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Désirée
authors.identifier: http://orcid.org/0000-0002-5781-158X
authors.initials: D
authors.lastname: van der Heijde
authors.affiliation: Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Atul
authors.identifier: http://orcid.org/0000-0002-2130-1246
authors.initials: A
authors.lastname: Deodhar
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
authors.forename: James C
authors.initials: JC
authors.lastname: Wei
authors.affiliation: Csolnoky Ferenc Hospital, Veszprém, Hungary.
authors.forename: Edit
authors.initials: E
authors.lastname: Drescher
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Dona
authors.initials: D
authors.lastname: Fleishaker
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Thijs
authors.initials: T
authors.lastname: Hendrikx
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: David
authors.initials: D
authors.lastname: Li
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Menon
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kanik
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D013167:Spondylitis, Ankylosing / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib
keywords: Ankylosing Spondylitis; Disease Activity; Magnetic Resonance Imaging; Treatment