Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed

Gastroenterology. 2014 Sep;147(3):618-627.e3. doi: 10.1053/j.gastro.2014.05.008. Epub 2014 May 21.


Background & aims: 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.

Keywords: Anti-TNF Therapy; Anti–α(4)β(7) Integrin; Lymphocyte Trafficking; Randomized Controlled Trial.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media
  • Webcast

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Crohn Disease / diagnosis
  • Crohn Disease / drug therapy*
  • Crohn Disease / immunology
  • Double-Blind Method
  • Drug Substitution*
  • Europe
  • Female
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / pharmacokinetics
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Israel
  • Male
  • Middle Aged
  • North America
  • Remission Induction
  • Time Factors
  • Treatment Failure
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult


  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • Gastrointestinal Agents
  • Tumor Necrosis Factor-alpha
  • vedolizumab

Associated data

  • ClinicalTrials.gov/NCT01224171