title: Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed.
abstract: OBJECTIVE
  There is an increasing need for new treatments for patients with Crohn's disease (CD) in whom previous therapy with tumor necrosis factor (TNF) antagonists has failed. We performed a placebo-controlled, phase 3, double-blind trial to evaluate the efficacy and safety of vedolizumab, an antibody against the integrin α4β7, as induction therapy.
  
  
  METHODS
  Patients with moderately to severely active CD (CD activity index [CDAI] score, 220-400 points) were assigned randomly to groups given vedolizumab (300 mg) or placebo intravenously at weeks 0, 2, and 6. The primary analysis involved 315 patients with previous TNF antagonist failure (ie, an inadequate response to, loss of response to, or intolerance of ≥1 TNF antagonists); we determined the proportion of patients in clinical remission (CDAI, ≤150 points) at week 6. Secondary analyses evaluated outcomes at weeks 6 and 10 in this population and in the overall population (N = 416), which included patients naive to TNF antagonist therapy (n = 101).
  
  
  RESULTS
  Among patients who had experienced previous TNF antagonist failure, 15.2% of those given vedolizumab and 12.1% of those given placebo were in remission at week 6 (P = .433). At week 10, a higher proportion of this population given vedolizumab was in remission (26.6%) than those given placebo (12.1%) (nominal P = .001; relative risk, 2.2; 95% confidence interval, 1.3-3.6). A higher proportion of patients with previous TNF antagonist failure given vedolizumab also had a CDAI-100 response (≥100-point decrease in CDAI score from baseline) at week 6 than those given placebo (39.2% vs 22.3%; nominal P = .001; relative risk, 1.8; 95% confidence interval, 1.2-2.5). Adverse event results were similar among all groups.
  
  
  CONCLUSIONS
  Vedolizumab was not more effective than placebo in inducing clinical remission at week 6 among patients with CD in whom previous treatment with TNF antagonists had failed. The therapeutic benefits of vedolizumab in these patients were detectable at week 10. ClinicalTrials.gov number: NCT01224171.
authors.affiliation: The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: bruce.sands@mssm.edu.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Sands
authors.affiliation: Robarts Clinical Trials Inc, and Robarts Research Institute, Department of Medicine, and Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Department of Gastroenterology, University Hospital Gasthuisberg and Katholieke Universiteit, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.affiliation: The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York; Département d'Hépato-Gastroentérologie et Centre d'Investigations Cliniques, Centre Hospitalier Régional Universitaire de Lille, Université Lille Nord de France, Lille, France.
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Division of Gastroenterology, University of California San Diego, La Jolla, California.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Department of Gastroenterology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Richmond
authors.initials: R
authors.lastname: Sy
authors.affiliation: Department of Gastroenterology, Inflammatory Bowel Disease Centre of the Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: Department of Gastroenterology, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shomron
authors.initials: S
authors.lastname: Ben-Horin
authors.affiliation: Takeda Pharmaceuticals International Co, Cambridge, Massachusetts.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Takeda Pharmaceuticals International Co, Cambridge, Massachusetts.
authors.forename: Maria
authors.initials: M
authors.lastname: Rosario
authors.affiliation: Takeda Pharmaceuticals International Co, Cambridge, Massachusetts.
authors.forename: Irving
authors.initials: I
authors.lastname: Fox
authors.affiliation: Takeda Pharmaceuticals International, Inc, Deerfield, Illinois.
authors.forename: Asit
authors.initials: A
authors.lastname: Parikh
authors.affiliation: Takeda Pharmaceuticals International Co, Cambridge, Massachusetts.
authors.forename: Catherine
authors.initials: C
authors.lastname: Milch
authors.affiliation: Division of Gastroenterology, The University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hanauer
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003424:Crohn Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D004311:Double-Blind Method; D057915:Drug Substitution; D005060:Europe; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007557:Israel; D008297:Male; D008875:Middle Aged; D009656:North America; D012074:Remission Induction; D013997:Time Factors; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; C543529:vedolizumab
keywords: Anti-TNF Therapy; Anti–α(4)β(7) Integrin; Lymphocyte Trafficking; Randomized Controlled Trial