Vedolizumab as induction and maintenance therapy for Crohn's disease.

Abstract

BACKGROUND:

The efficacy of vedolizumab, an α4β7 integrin antibody, in Crohn's disease is unknown.

METHODS:

In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52.

RESULTS:

At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of ≤150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (≥100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P<0.001 and P=0.004 for the two vedolizumab groups, respectively, vs. placebo). Antibodies against vedolizumab developed in 4.0% of the patients. Nasopharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving vedolizumab than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%).

CONCLUSIONS:

Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolizumab (rather than switching to placebo) were more likely to be in remission at week 52. Adverse events were more common with vedolizumab. (Funded by Millennium Pharmaceuticals; GEMINI 2 ClinicalTrials.gov number, NCT00783692.).

• Authors: William J Sandborn, Brian G Feagan, Paul Rutgeerts, Stephen Hanauer, Jean-Frédéric Colombel, Bruce E Sands, Milan Lukas, Richard N Fedorak, Scott Lee, Brian Bressler, Irving Fox, Maria Rosario, Serap Sankoh, Jing Xu, Kristin Stephens, Catherine Milch, Asit Parikh, GEMINI 2 Study Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 369 Issue 8 Pg. 711-21 (Aug 22 2013) ISSN: 1533-4406 [Electronic] United States
• PMID: 23964933 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Antibodies, Monoclonal, Humanized
• Glucocorticoids
• Immunosuppressive Agents
• Integrins
• integrin alpha4beta7
• vedolizumab

Topics

• Adult
• Antibodies (blood)
• Antibodies, Monoclonal, Humanized (adverse effects, immunology, therapeutic use)
• Crohn Disease (drug therapy)
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Glucocorticoids (therapeutic use)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Induction Chemotherapy
• Infusions, Intravenous (adverse effects)
• Integrins (antagonists & inhibitors, immunology)
• Maintenance Chemotherapy
• Male
• Middle Aged