title: Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials.
abstract: Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD).
  
  
  
  We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study.
  
  
  
  180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (p<0.0001) with 10 mg twice daily after both induction and maintenance treatments.
  
  
  
  Primary efficacy endpoints were not significantly different from placebo, although there was evidence of a minor treatment effect. No new safety signals were observed for tofacitinib.
  
  
  
  NCT01393626 and NCT01393899.
authors.affiliation: Hospital Clinic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Julian
authors.initials: J
authors.lastname: Panés
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Klinik für Innere Medizin I, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.affiliation: Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Sands
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Remo
authors.initials: R
authors.lastname: Panaccione
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Peter D R
authors.initials: PDR
authors.lastname: Higgins
authors.affiliation: Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Robarts Research Institute, London, Ontario, Canada.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Chan
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Moscariello
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Wenjin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Niezychowski
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Marren
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Healey
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Maller
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D012074:Remission Induction; D012720:Severity of Illness Index
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D002097:C-Reactive Protein
keywords: CLINICAL TRIALS; CROHN'S DISEASE; IMMUNOLOGY