title: Efficacy of Vedolizumab Induction and Maintenance Therapy in Patients With Ulcerative Colitis, Regardless of Prior Exposure to Tumor Necrosis Factor Antagonists.
abstract: The efficacy and safety of vedolizumab, a humanized immunoglobulin G1 monoclonal antibody against the integrin α4β7, were demonstrated in multicenter, phase 3, randomized, placebo-controlled trials in patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease. We analyzed data from 1 of these trials to determine the effects of vedolizumab therapy in patients with UC, based on past exposure to anti-tumor necrosis factor-α (TNF) antagonists.
  
  
  
  We performed a post hoc analysis of data from the GEMINI 1 study, collected from 464 patients who received vedolizumab or placebo but had not received a previous TNF antagonist (naive to TNF antagonists) and 367 patients with an inadequate response, loss of response, or intolerance to TNF antagonists (failure of TNF antagonists). Predefined outcomes of GEMINI 1 were evaluated in these subpopulations.
  
  
  
  At Week 6, there were greater absolute differences in efficacy between vedolizumab and placebo in patients naive to TNF antagonists than patients with failure of TNF antagonists, although the risk ratios (RRs) for efficacy were similar for each group. Week 6 rates of response to vedolizumab and placebo were 53.1% and 26.3%, respectively, among patients naive to TNF antagonists (absolute difference, 26.4%; 95% confidence interval [CI], 12.4-40.4; RR, 2.0; 95% CI, 1.3-3.0); these rates were 39.0% and 20.6%, respectively, in patients with failure of TNF antagonists (absolute difference, 18.1%; 95% CI, 2.8-33.5; RR, 1.9; 95% CI, 1.1-3.2). During maintenance therapy, the absolute differences were similar but the RR for efficacy was higher for patients with failure of TNF antagonists than for patients naive to TNF antagonists, for most outcomes. Week 52 rates of remission with vedolizumab and placebo were 46.9% and 19.0%, respectively, in patients naive to TNF antagonists (absolute difference, 28.0%; 95% CI, 14.9-41.1; RR, 2.5; 95% CI, 1.5-4.0) and 36.1% and 5.3%, respectively, in patients with failure of TNF antagonists (absolute difference, 29.5%; 95% CI, 12.8-46.1; RR, 6.6; 95% CI, 1.7-26.5). No differences in adverse events were observed among groups.
  
  
  
  Vedolizumab demonstrated significantly greater efficacy as induction and maintenance therapy for UC than placebo in patients naive to TNF antagonists and patients with TNF antagonist failure. There were numerically greater treatment differences at Week 6 among patients receiving vedolizumab who were naive to TNF antagonists than patients with TNF antagonist failure. ClinicalTrials.gov no: NCT00783718.
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada. Electronic address: bfeagan@robarts.ca.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois.
authors.forename: David T
authors.initials: DT
authors.lastname: Rubin
authors.affiliation: Istituto Clinico Humanitas, Milan, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Danese
authors.affiliation: University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Takeda Development Centre Europe Ltd, London, United Kingdom.
authors.forename: Brihad
authors.initials: B
authors.lastname: Abhyankar
authors.affiliation: Takeda Pharmaceuticals International Co, Cambridge, Massachusetts.
authors.forename: Serap
authors.initials: S
authors.lastname: Sankoh
authors.affiliation: Takeda Development Centre Europe Ltd, London, United Kingdom.
authors.forename: Alexandra
authors.initials: A
authors.lastname: James
authors.affiliation: Takeda Development Centre Europe Ltd, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Smyth
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005765:Gastrointestinal Agents; D010919:Placebos; C543529:vedolizumab
keywords: Biologic-Naive; GEMINI; Inflammatory Bowel Disease; Treatment Failure