The safety of vedolizumab for ulcerative colitis and Crohn's disease

Gut. 2017 May;66(5):839-851. doi: 10.1136/gutjnl-2015-311079. Epub 2016 Feb 18.

Abstract

Objective: Vedolizumab is a gut-selective antibody to α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). We report an integrated summary of the safety of vedolizumab.

Design: Safety data (May 2009-June 2013) from six trials of vedolizumab were integrated. Adverse events were evaluated in patients who received ≥1 dose of vedolizumab or placebo and were reported as exposure-adjusted incidence rates as the number of patients experiencing the event per 100 person-years (PYs) of exposure. Predictors of serious infection were assessed using a Cox proportional hazards model.

Results: In total, 2830 patients had 4811 PYs of vedolizumab exposure (median exposure range, 1-1977 days). No increased risk of any infection or serious infection was associated with vedolizumab exposure. Serious clostridial infections, sepsis and tuberculosis were reported infrequently (≤0.6% of patients). No cases of progressive multifocal leucoencephalopathy were observed. Independent risk factors for serious infection in UC were prior failure of a tumour necrosis factor α antagonist (HR, 1.99; 95% CIs 1.16 to 3.42; p=0.0122) and narcotic analgesic use (HR, 2.68; 95% CI 1.57 to 4.58; p=0.0003), and in CD were younger age (HR, 0.97; 95% CI 0.95 to 0.98; p<0.0001), corticosteroid (HR, 1.88; 95% CI 1.35 to 2.63; p=0.0002) or narcotic analgesic use (HR, 2.72; 95% CI 1.90 to 3.89; p<0.0001). Investigator-defined infusion-related reactions were reported for ≤5% of patients in each study. Eighteen vedolizumab-exposed patients (<1%) were diagnosed with a malignancy.

Conclusions: Vedolizumab has a favourable safety profile with low incidence rates of serious infections, infusion-related reactions and malignancies over an extended treatment period.

Trial registration number: NCT01177228, NCT00619489, NCT00783718, NCT00783692, NCT01224171, NCT00790933.

Keywords: INFLAMMATORY BOWEL DISEASE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Age Factors
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / immunology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antibodies, Neutralizing / blood
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Clostridium Infections / epidemiology*
  • Colitis, Ulcerative / drug therapy
  • Crohn Disease / drug therapy
  • Female
  • Gastrointestinal Agents / adverse effects*
  • Gastrointestinal Agents / immunology
  • Gastrointestinal Agents / therapeutic use
  • Humans
  • Incidence
  • Infusions, Intravenous / adverse effects
  • Leukoencephalopathy, Progressive Multifocal / epidemiology
  • Male
  • Middle Aged
  • Narcotics / therapeutic use
  • Neoplasms / epidemiology*
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Sepsis / epidemiology*
  • Treatment Failure
  • Tuberculosis / epidemiology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Gastrointestinal Agents
  • Narcotics
  • Tumor Necrosis Factor-alpha
  • vedolizumab

Associated data

  • ClinicalTrials.gov/NCT01224171
  • ClinicalTrials.gov/NCT00783718
  • ClinicalTrials.gov/NCT00783692
  • ClinicalTrials.gov/NCT01177228
  • ClinicalTrials.gov/NCT00790933
  • ClinicalTrials.gov/NCT00619489