title: Vedolizumab as induction and maintenance therapy for ulcerative colitis.
abstract: BACKGROUND
  Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis.
  
  
  METHODS
  We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.
  
  
  RESULTS
  Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P<0.001). At week 52, 41.8% of patients who continued to receive vedolizumab every 8 weeks and 44.8% of patients who continued to receive vedolizumab every 4 weeks were in clinical remission (Mayo Clinic score ≤2 and no subscore >1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups.
  
  
  CONCLUSIONS
  Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.).
authors: Robarts Clinical Trials, Robarts Research Institute, and Department of Medicine, University of Western Ontario, London, Canada. bfeagan@robarts.ca
authors: Brian G
authors: BG
authors: Feagan
authors: Paul
authors: P
authors: Rutgeerts
authors: Bruce E
authors: BE
authors: Sands
authors: Stephen
authors: S
authors: Hanauer
authors: Jean-Frédéric
authors: JF
authors: Colombel
authors: William J
authors: WJ
authors: Sandborn
authors: Gert
authors: G
authors: Van Assche
authors: Jeffrey
authors: J
authors: Axler
authors: Hyo-Jong
authors: HJ
authors: Kim
authors: Silvio
authors: S
authors: Danese
authors: Irving
authors: I
authors: Fox
authors: Catherine
authors: C
authors: Milch
authors: Serap
authors: S
authors: Sankoh
authors: Tim
authors: T
authors: Wyant
authors: Jing
authors: J
authors: Xu
authors: Asit
authors: A
authors: Parikh
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D060828:Induction Chemotherapy; D016023:Integrins / Q000037:antagonists & inhibitors / Q000276:immunology*; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016023:Integrins; C071777:integrin alpha4beta7; C543529:vedolizumab