title: Clinical remission in patients with moderate-to-severe Crohn's disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial.
abstract: Filgotinib (GLPG0634, GS-6034) is a once-daily, orally administered, Janus kinase 1 (JAK1)-selective inhibitor. The FITZROY study examined the efficacy and safety of filgotinib for the treatment of moderate-to-severe Crohn's disease.
  
  
  
  We did a randomised, double-blind, placebo-controlled phase 2 study, which recruited patients from 52 centres in nine European countries. We enrolled eligible patients aged 18-75 years with a documented history of ileal, colonic, or ileocolonic Crohn's disease for 3 months or more before screening, as assessed by colonoscopy and supported by histology, and a Crohn's Disease Activity Index (CDAI) score during screening between 220 and 450 inclusive. Patients were randomly assigned (3:1) to receive filgotinib 200 mg once a day or placebo for 10 weeks. Patients were stratified according to previous anti-tumour necrosis factor alpha exposure, C-reactive protein concentration at screening (≤10 mg/L or >10 mg/L), and oral corticosteroid use at baseline, using an interactive web-based response system. The primary endpoint was clinical remission, defined as CDAI less than 150 at week 10. After week 10, patients were assigned based on responder status to filgotinib 100 mg once a day, filgotinib 200 mg once a day, or placebo for an observational period lasting a further 10 weeks. The filgotinib and placebo treatment groups were compared using ANCOVA models and logistic regression models containing baseline values and randomisation stratification factors as fixed effects. Analyses were done on the intention-to-treat non-responder imputation set. The trial was registered at ClinicalTrials.gov, number NCT02048618.
  
  
  
  Between Feb 3, 2014, and July 10, 2015, we enrolled 174 patients with active Crohn's disease confirmed by centrally read endoscopy (130 in the filgotinib 200 mg group and 44 in the placebo group). In the intention-to-treat population, 60 (47%) of 128 patients treated with filgotinib 200 mg achieved clinical remission at week 10 versus ten (23%) of 44 patients treated with placebo (difference 24 percentage points [95% CI 9-39], p=0·0077). In a pooled analysis of all periods of filgotinib and placebo exposure over 20 weeks, serious treatment-emergent adverse effects were reported in 14 (9%) of 152 patients treated with filgotinib and three (4%) of 67 patients treated with placebo.
  
  
  
  Filgotinib induced clinical remission in significantly more patients with active Crohn's disease compared with placebo, and had an acceptable safety profile.
  
  
  
  Galapagos.
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium. Electronic address: severine.vermeire@uzleuven.be.
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: University Hospital Schleswig-Holstein and Institute for Clinical Molecular Biology, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.affiliation: NZOZ ViVamed, Zamiejska 17, 03-580, Warsaw, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Petryka
authors.affiliation: Department of Gastroenterology, Asklepios Westklinikum, Hamburg, Germany; Christian Albrecht University, Kiel, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kuehbacher
authors.affiliation: Department of Gastroenterology and Nutrition, Archet 2 Hospital, Le Centre Hospitalier Universitaire de Nice, and University Côte d'Azur, Nice, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Hebuterne
authors.affiliation: Department of Gastroenterology, University Hospital of Saint Etienne, Saint Etienne, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Roblin
authors.affiliation: NC University in Toruń, Collegium Medicum in Bydgoszcz, Department of Vascular Diseases and Internal Medicine, Bydgoszcz, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Klopocka
authors.affiliation: University of Medicine Timisoara, Clinic of Gastroenterology, Timisoara, Romania.
authors.forename: Adrian
authors.initials: A
authors.lastname: Goldis
authors.affiliation: Department of Gastroenterology, Medical University of Lodz and Saint Family Medical Centre of Lodz, Lodz, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Wisniewska-Jarosinska
authors.affiliation: Center of Gastroenterology and Hepatology, Medical Faculty, Saint-Petersburg State University, St Petersburg, Russia.
authors.forename: Andrey
authors.initials: A
authors.lastname: Baranovsky
authors.affiliation: Szent Margit Hospital Department of Gastroenterology, Budapest, Hungary.
authors.forename: Robert
authors.initials: R
authors.lastname: Sike
authors.affiliation: PSI Pharma Support EOOD, Sofia, Bulgaria.
authors.forename: Kremena
authors.initials: K
authors.lastname: Stoyanova
authors.affiliation: Galapagos NV, Generaal De Wittelaan L11A3, Mechelen, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Tasset
authors.affiliation: Galapagos NV, Generaal De Wittelaan L11A3, Mechelen, Belgium.
authors.forename: Annegret
authors.initials: A
authors.lastname: Van der Aa
authors.affiliation: Galapagos NV, Generaal De Wittelaan L11A3, Mechelen, Belgium.
authors.forename: Pille
authors.initials: P
authors.lastname: Harrison
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000075242:Janus Kinase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: C584571:GLPG0634; D000075242:Janus Kinase Inhibitors; D011725:Pyridines; D014230:Triazoles