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Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease

Published on Apr 27, 2017in Alimentary Pharmacology & Therapeutics7.731
· DOI :10.1111/APT.14075
W. A. Bye1
Estimated H-index: 1
(John Radcliffe Hospital),
Vipul Jairath17
Estimated H-index: 17
(UWO: University of Western Ontario),
Simon P.L. Travis6
Estimated H-index: 6
(John Radcliffe Hospital)
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Abstract
SummaryBackground Vedolizumab specifically recognises the α4β7 integrin and selectively blocks gut lymphocyte trafficking: potentially, it offers gut-specific immunosuppression. Aim To review the safety of vedolizumab and summarise post-marketing data to assess if any safety concerns that differ from registration trials have emerged. Method A systematic bibliographic search identified six registration trials and nine cohort studies. Results Integrated data from registration trials included 2830 vedolizumab-exposed patients (4811 person-years exposure [PYs]) and 513 placebo patients. This reported lower exposure-adjusted incidence rates of infection (63.5/100 PYs; 95% CI: 59.6-67.3) and serious adverse events (20.0/100 PYs; 95% CI: 18.5-21.5) compared to placebo (82.9/100 PYs; 95% CI: 68.3-97.5) and (28.3/100 PYs 95% CI: 20.6-35.9) respectively. Higher, but statistically insignificant rates of enteric infections occurred in vedolizumab-exposed patients (7.4/100 PYs; 95% CI: 6.6-8.3) compared to placebo (6.7 PYs; 95% CI: 3.2-10.1). Six post-marketing cohort studies (1049 patients, 403 PYs) demonstrated rates of infection of 8% (82/1049); enteric infection of 2% (21/1049) and adverse events of 16% (166/1049). Multivariate analysis in one cohort study suggested increased risk of surgical site infection with perioperative VDZ. Human experience in pregnancy is limited. Conclusions Post-marketing data confirm the excellent safety of vedolizumab observed in registration trials. The signal of post-operative complications should be interpreted with caution, but warrants further study. Although comparative studies are needed, Vedolizumab may be a safe alternative in patients who best avoid systematic immunosuppression, including those pre-disposed to infection, malignancy or the elderly.
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References48
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#1Paweł Moćko (Jagiellonian University)H-Index: 3
Last. Andrzej Pilc (PAN: Polish Academy of Sciences)H-Index: 51
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Background and Objectives Biologic drugs are used in innovative therapies for the management of inflammatory bowel diseases (IBDs). The aim of this study was to compare the safety profile of biologic drugs in patients with IBD.
9 CitationsSource
#1Maire A. Conrad (Children's Hospital of Philadelphia)H-Index: 6
#2Ronen Stein (Children's Hospital of Philadelphia)H-Index: 4
Last. Judith R. Kelsen (UPenn: University of Pennsylvania)H-Index: 19
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Vedolizumab is effective for inducing and maintaining remission in adults with inflammatory bowel disease (IBD); however, there is limited pediatric data. This study aimed to describe the adverse events and clinical response to vedolizumab in refractory pediatric IBD.Disease activity indices, clinical response, concomitant medication use, and adverse events were measured over 22 weeks in an observational prospective cohort study of children with refractory IBD who had failed anti-tumor necrosis ...
32 CitationsSource
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#2Shervin Rabizadeh (Cedars-Sinai Medical Center)H-Index: 11
Last. Marla Dubinsky (Mount Sinai Hospital)H-Index: 61
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BACKGROUND: Though vedolizumab has received regulatory approval for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) in adults, there is increasing off-label use in children. AIMS: To describe the experience with vedolizumab in pediatric inflammatory bowel disease (IBD) patients at 3 tertiary IBD centers and examine predictors of remission. METHODS: A retrospective review identified pediatric IBD patients (age < 18 yrs) receiving vedolizumab. Data on demographics, disease behavi...
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Background and Objectives Vedolizumab, a humanized monoclonal antibody against the α4β7 integrin, is indicated for treatment of moderately to severely active ulcerative colitis or Crohn’s disease. In this placebo-controlled, double-blind, randomized, single ascending-dose study, the pharmacokinetics, pharmacodynamics, safety, and tolerability of vedolizumab were evaluated in healthy volunteers.
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Background Vedolizumab (VDZ) is a humanised monoclonal IgG1 antibody targeting alpha(4)beta(7) integrin. Aim To investigate the real-world efficacy of vedolizumab for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Methods A consecutive cohort of 212 adult IBD patients with active disease (HBI > 7/ partial Mayo > 4) newly receiving VDZ was prospectively recruited from 7 academic and 17 community centres. The primary endpoint was clinical remission (CRM) (CD HBI <= 4, UC pMayo ...
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Background Vedolizumab is a monoclonal antibody approved for use in ulcerative colitis and Crohn's disease. By specifically binding to α4β7 integrin, vedolizumab prevents trafficking of lymphocytes to the gut, thereby interfering with disease pathology. During the clinical development program, the pharmacodynamic effect of vedolizumab was evaluated by 2 flow cytometry receptor occupancy assays: act-1 (ACT-1) and mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Here we describe the developm...
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Background and aims: Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn’s disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. Methods: Patients beginning vedolizumab were enrolled with informed consent. A pros...
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Resume Les maladies inflammatoires chroniques de l’intestin (MICI) sont des pathologies touchant les patientes en âge de procreer. Le defaut d’information de ses patientes est responsable d’une infertilite volontaire mais aussi d’une mauvaise observance des traitements en cours de grossesse. L’objectif de ce travail est de faire une mise au point sur les liens entre les MICI et la grossesse de la conception a l’accouchement. L’activite de la maladie joue un role majeur. En cas de maladie non act...
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Resume Les maladies inflammatoires chroniques de l’intestin (MICI) sont des pathologies touchant les patientes en âge de procreer. Le defaut d’information de ces patientes est responsable d’une infertilite volontaire mais aussi d’une mauvaise observance des traitements en cours de grossesse. L’objectif de ce travail est de faire une mise au point sur les liens entre les MICI et la grossesse de la conception a l’accouchement. L’activite de la maladie joue un role majeur. En cas de maladie non act...
Source