title: Efficacy of VX-509 (decernotinib) in combination with a disease-modifying antirheumatic drug in patients with rheumatoid arthritis: clinical and MRI findings.
abstract: OBJECTIVE
  To assess early effects on joint structures of VX-509 in combination with stable disease-modifying antirheumatic drug (DMARD) therapy using MRI in adults with rheumatoid arthritis (RA).
  
  
  METHODS
  This phase II, placebo-controlled, double-blind, dose-ranging study randomised patients with RA and inadequate DMARD response to VX-509 100 mg (n=11), 200 mg (n=10) or 300 mg (n=10) or placebo (n=12) once daily for 12 weeks. Outcome measures included American College of Rheumatology score (ACR20; improvement of ≥20%) and disease activity score (DAS28) using C reactive protein (CRP), and the RA MRI scoring (RAMRIS) system.
  
  
  RESULTS
  ACR20 response at week 12 was 63.6%, 60.0% and 60.0% in the VX-509 100-mg, 200-mg and 300-mg groups, respectively, compared with 25.0% in the placebo group. DAS28-CRP scores decreased in a dose-dependent manner with increasing VX-509 doses. Decreases in RAMRIS synovitis scores were significantly different from placebo for all VX-509 doses (p<0.01) and for RAMRIS osteitis scores (p<0.01) for VX-509 300 mg. Treatment was generally well tolerated.
  
  
  CONCLUSIONS
  VX-509 plus a DMARD reduced the signs and symptoms of RA in patients with an inadequate response to a DMARD alone. MRI responses were detected at week 12. Treatment was generally well tolerated.
  
  
  BACKGROUND
  NCT01754935; results.
authors.affiliation: Division of Immunology and Rheumatology, Stanford University, Palo Alto, California, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Genovese
authors.affiliation: Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet-Glostrup, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
authors.affiliation: Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA.
authors.forename: Nils
authors.initials: N
authors.lastname: Kinnman
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006574:Heterocyclic Compounds, 2-Ring / Q000008:administration & dosage*; D006801:Humans; D007596:Joints / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: C000596981:2-((2-(1H-pyrrolo(2,3-b)pyridin-3-yl)pyrimidin-4-yl)amino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide; D018501:Antirheumatic Agents; D006574:Heterocyclic Compounds, 2-Ring; D014633:Valine
keywords: DMARDs (biologic); Magnetic Resonance Imaging; Rheumatoid Arthritis