title: The safety of vedolizumab for ulcerative colitis and Crohn's disease.
abstract: Vedolizumab is a gut-selective antibody to α4β7integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). We report an integrated summary of the safety of vedolizumab.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Vedolizumab has a favourable safety profile with low incidence rates of serious infections, infusion-related reactions and malignancies over an extended treatment period.
  
  
  
  NCT01177228, NCT00619489, NCT00783718, NCT00783692, NCT01224171, NCT00790933.
authors.affiliation: Division of Gastroenterology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York, USA.
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Division of Gastroenterology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Sands
authors.affiliation: Division of Gastroenterology, Katholieke Universiteit and University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.affiliation: Division of Gastroenterology, University of California San Diego and UC San Diego Health System, La Jolla, California, USA.
authors.forename: William
authors.initials: W
authors.lastname: Sandborn
authors.affiliation: Department of Gastroenterology, Istituto Clinico Humanitas, Milan, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Danese
authors.affiliation: Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Remo
authors.initials: R
authors.lastname: Panaccione
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Edward V
authors.initials: EV
authors.lastname: Loftus
authors.affiliation: Takeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA.
authors.forename: Serap
authors.initials: S
authors.lastname: Sankoh
authors.affiliation: Takeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA.
authors.forename: Irving
authors.initials: I
authors.lastname: Fox
authors.affiliation: Takeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA.
authors.forename: Asit
authors.initials: A
authors.lastname: Parikh
authors.affiliation: Takeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Milch
authors.affiliation: Takeda Global Research and Development Centre (Europe) Ltd., London, UK.
authors.forename: Brihad
authors.initials: B
authors.lastname: Abhyankar
authors.affiliation: Department of Medicine, Robarts Clinical Trials, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000367:Age Factors; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology; D003015:Clostridium Infections / Q000453:epidemiology*; D003093:Colitis, Ulcerative / Q000188:drug therapy; D003424:Crohn Disease / Q000188:drug therapy; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D007262:Infusions, Intravenous / Q000009:adverse effects; D007968:Leukoencephalopathy, Progressive Multifocal / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009294:Narcotics / Q000627:therapeutic use; D009369:Neoplasms / Q000453:epidemiology*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D018805:Sepsis / Q000453:epidemiology*; D017211:Treatment Failure; D014376:Tuberculosis / Q000453:epidemiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D005765:Gastrointestinal Agents; D009294:Narcotics; D014409:Tumor Necrosis Factor-alpha; C543529:vedolizumab
keywords: INFLAMMATORY BOWEL DISEASE