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

Jean-Frédéric Colombel, Bruce E Sands, Paul Rutgeerts, William Sandborn, Silvio Danese, Geert D'Haens, Remo Panaccione, Edward V Loftus, Serap Sankoh, Irving Fox, Asit Parikh, Catherine Milch, Brihad Abhyankar, Brian G Feagan

Journal: Gut 2017;66(5):839-851

PMID: 26893500

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Abstract

OBJECTIVE

Vedolizumab is a gut-selective antibody to αβ 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.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Address: Division of Gastroenterology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York, USA.; Division of Gastroenterology, Katholieke Universiteit and University Hospital Gasthuisberg, Leuven, Belgium.; Division of Gastroenterology, University of California San Diego and UC San Diego Health System, La Jolla, California, USA.; Department of Gastroenterology, Istituto Clinico Humanitas, Milan, Italy.; Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.; Department of Medicine, University of Calgary, Calgary, Alberta, Canada.; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.; Takeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA.; Takeda Global Research and Development Centre (Europe) Ltd., London, UK.; Department of Medicine, Robarts Clinical Trials, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.

DOI: 10.1136/gutjnl-2015-311079