Gastroenterology

Gastroenterology

Volume 147, Issue 3, September 2014, Pages 618-627.e3
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Effects of Vedolizumab Induction Therapy for Patients With Crohn’s Disease in Whom Tumor Necrosis Factor Antagonist Treatment Failed

https://doi.org/10.1053/j.gastro.2014.05.008Get rights and content
Under a Creative Commons license
open access

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–α4β7 Integrin
Anti-TNF Therapy
Randomized Controlled Trial
Lymphocyte Trafficking

Abbreviations used in this paper

AE
adverse event
CD
Crohn’s disease
CDAI
Crohn’s Disease Activity Index
CDAI-100
CDAI score decrease of 100 points or more from baseline
CI
confidence interval
CNS
central nervous system
CRP
C-reactive protein
MAdCAM-1
mucosal addressin cell adhesion molecule-1
PML
progressive multifocal leukoencephalopathy
SAE
serious adverse event
TNF
tumor necrosis factor
UC
ulcerative colitis

Cited by (0)

Conflicts of interest The authors disclose the following: Bruce Sands has received consulting and advisory board fees as well as clinical research/institutional grant support from AbbVie, Inc, Janssen Pharmaceuticals, Inc, and Takeda Pharmaceuticals International Co; Brian Feagan has received consulting fees and research grant support from Janssen Pharmaceuticals, Inc, Takeda Pharmaceuticals International Co, and UCB SA; Paul Rutgeerts has received consulting fees from Takeda Pharmaceuticals International Co. and UCB SA; Jean-Frédéric Colombel has received consulting fees from Takeda Pharmaceuticals International Co. and UCB SA; William Sandborn has received consulting fees and research grants from Janssen Pharmaceuticals, Inc, Takeda Pharmaceuticals International Co, and UCB SA, and speaker fees from Janssen Pharmaceuticals, Inc; Richmond Sy has received consulting, lecture, and advisory board fees as well as research grant support from AbbVie, Inc, and Janssen Pharmaceuticals, Inc, and both advisory board fees and clinical trial support from Takeda Pharmaceuticals International Co; Geert D'Haens has received consulting and lecture fees from AbbVie, Inc, Janssen Pharmaceuticals, Inc, Takeda Pharmaceuticals International Co, and UCB SA, research grants from Janssen Pharmaceuticals, Inc, and speaking honoraria from UCB SA; Shomron Ben-Horin has received consultancy and advisory board fees from Janssen Pharmaceuticals, Inc, and AbbVie, Inc, and an unrestricted research grant from Janssen Pharmaceuticals, Inc; Asit Parikh is an employee of Takeda Pharmaceuticals International, Inc; Jing Xu, Maria Rosario, Irving Fox, and Catherine Milch are employees of Takeda Pharmaceuticals International Co; and Stephen Hanauer has received consultancy and advisory board fees as well as clinical research/institutional grant support from AbbVie, Inc, Janssen Pharmaceuticals, Inc, Takeda Pharmaceuticals International Co, and UCB SA.

Funding Sponsored and funded by Millennium Pharmaceuticals, Inc (doing business as Takeda Pharmaceuticals International Co).

Author names in bold designate co-first authors.