title: VX-509 (Decernotinib), an Oral Selective JAK-3 Inhibitor, in Combination With Methotrexate in Patients With Rheumatoid Arthritis.
abstract: OBJECTIVE
  To assess the efficacy and safety of decernotinib (VX-509), an oral selective inhibitor of JAK-3, in patients with rheumatoid arthritis (RA) in whom the response to methotrexate treatment was inadequate.
  
  
  METHODS
  In this 24-week, double-blind, randomized phase IIb study, 358 patients with active RA received either placebo (n = 71) or VX-509 at dosages of 100 mg/day (n = 71), 150 mg/day (n = 72), 200 mg/day (n = 72), or 100 mg twice daily (n = 72). Primary measures of efficacy at week 12 were the response rate according to the American College of Rheumatology 20% improvement criteria (ACR20) and change from baseline in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP).
  
  
  RESULTS
  At week 12, the ACR20 response rates were 46.5%, 66.7%, 56.9%, and 68.1% in the groups receiving VX-509 at dosages of 100 mg/day, 150 mg/day, 200 mg/day, and 100 mg twice daily, respectively, and 18.3% in the placebo group (P < 0.001 for all comparisons). At week 12, the mean change from baseline in the DAS28-CRP was significantly greater in each VX-509 group compared with the placebo group (P < 0.001). Improvements were maintained at week 24, as shown by the ACR20, ACR50, and ACR70 response rates and mean change from baseline in the DAS28-CRP. The most common adverse event in the VX-509 group was headache (8.7%), and elevated levels of transaminases, lipoproteins, and creatinine were observed.
  
  
  CONCLUSIONS
  VX-509 significantly improved the signs and symptoms of RA at weeks 12 and 24 compared with the placebo group when it was administered in combination with methotrexate. Safety signals included infection and increases in liver transaminase and lipid levels.
authors.affiliation: Stanford University, Palo Alto, California.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Genovese
authors.affiliation: Karolinska Institute, Stockholm, Sweden.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.affiliation: Universidad Autónoma de Chihuahua, Chihuahua, Mexico.
authors.forename: César
authors.initials: C
authors.lastname: Pacheco-Tena
authors.affiliation: Vertex Pharmaceuticals Incorporated, Boston, Massachusetts.
authors.forename: Yanqiong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Vertex Pharmaceuticals Incorporated, Boston, Massachusetts.
authors.forename: Nils
authors.initials: N
authors.lastname: Kinnman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001219:Aspartate Aminotransferases / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006261:Headache / Q000139:chemically induced; D006574:Heterocyclic Compounds, 2-Ring / Q000627:therapeutic use*; D006801:Humans; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
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; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006574:Heterocyclic Compounds, 2-Ring; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053616:Janus Kinase 3; D014633:Valine; D008727:Methotrexate