Effectiveness and Safety of Vedolizumab Induction Therapy for Patients with Inflammatory Bowel Disease

Aurelien Amiot (1, 2) , Jean-Charles Grimaud (3) , Laurent Peyrin-Biroulet (4) , Jérome Filippi (5) , Benjamin Pariente (6) , Xavier Roblin (7) , Anthony Buisson (8) , Carmen Stefanescu (9, 10) , Caroline Trang-Poisson (11) , Romain Altwegg (12) , Philippe Marteau (13) , Thibaud Vaysse (14) , Anne Bourrier (15, 16) , Stéphane Nancey (17, 18) , David Laharie (19) , Matthieu Allez (20) , Guillaume Savoye (21, 22, 23) , Jacques Moreau (24) , Charlotte Gagniere (1, 2) , Lucine Vuitton (25) , Stephanie Viennot (26) , Alexandre Aubourg (27, 28) , Anne-Laure Pelletier (29) , Guillaume Bouguen (30, 31, 32) , Vered Abitbol (33) , Yoram Bouhnik (9, 10) , Camille Zallot (4) , Marc-André Bigard (4) , Xavier Hebuterne (34, 5) , Maria Nachury (35) , Pierre Desreumaux (6, 36, 37) , Emilie del Tedesco (38) , Gilles Bommelaer (36) , Arnaud Boureille (39) , Xavier Dray (40, 13) , Franck Carbonnel (41) , Philippe Seksik (42) , Laurent Beaugerie (42) , Jacques Cosnes (15, 16) , Harry Sokol (42, 43) , Cecilia Landman (15, 16) , Gilles Boschetti (44) , Florian Poullenot (45) , Jean-Marc Gornet (20) , Clautilde Baudry (46) , Stéphane Koch (47) , Laurence Picon (48) , Gaelle Sickersen (49) , Stanislas Chaussade (50) , Stephane Nahon (51) , Betsy Winkfield (52, 53) , Hedia Brixi-Benmansour (53) , Rodica Gincul (54) , Jean-Christophe Barberis (52) , Bruno Bonaz (55) , Christophe Michiels (52) , Franck Zerbib (19) , Marie Bourrier De Beauregard (52) , Christophe Locher (56) , Sophie Davin-Couve (52) , Armelle Poirette (52) , Laurence Guillem (52) , Monica Stetiu-Mocanu (52) , Sylvain Beorchia (52) , Jawad Al Qaddi (52)

1 LIC - Laboratoire d'Investigation Clinique
2 EC2M3 - Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375)
3 AMU MED - Aix-Marseille Université - Faculté de médecine
4 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
5 CHU Nice - Centre Hospitalier Universitaire de Nice
6 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
7 CHU de Saint-Etienne - Centre Hospitalier Universitaire de Saint-Etienne
8 CHU Clermont-Ferrand
9 Service de Gastroentérologie [Hôpital Beaujon]
10 UPD7 - Université Paris Diderot - Paris 7
11 Institut des Maladies de l'Appareil Digestif
12 Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi]
13 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
14 Service de neurologie [Le Kremlin Bicêtre]
15 Service de Gastroentérologie et nutrition [CHU Saint-Antoine]
16 Service de rhumatologie [CHU Saint-Antoine]
17 HCL - Hospices Civils de Lyon
18 UCBL - Université Claude Bernard Lyon 1
19 Service d'Hépato-Gastro-Entérologie
20 AP-HP - Hopital Saint-Louis [AP-HP]
21 ADEN - Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau
22 UNIROUEN - Université de Rouen Normandie
23 IRIB - Institute for Research and Innovation in Biomedicine
24 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
25 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
26 Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen]
27 GICC UMR 7292 CNRS - Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017]
28 CHU Trousseau [Tours]
29 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
30 Foie, métabolismes et cancer
31 Hôpital Pontchaillou
32 UR - Université de Rennes
33 AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
34 UNS - Université Nice Sophia Antipolis (1965 - 2019)
35 Hôpital Claude Huriez [Lille]
36 INSERM - Institut National de la Santé et de la Recherche Médicale
37 Université de Lille, Droit et Santé
38 Service d'Hépato-gastroentérologie [CHU Saint-Etienne]
39 Neuropathies du système nerveux entérique et pathologies digestives; implication des cellules gliales entériques
40 ASTRE [Cergy-Pontoise]
41 AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
42 CHU Saint-Antoine [AP-HP]
43 CRSA - Centre de Recherche Saint-Antoine
44 Service d'Hépatologie et de Gastroentérologie [Lyon]
45 Hôpital Haut-Lévêque [CHU Bordeaux]
46 Service d'Endocrinologie, Diabétologie, Maladies Métaboliques, Hôpital Avicenne
47 Wallenberg Centre for Molecular Medicine (WCMM)
48 Hépato-Gastro-Onco-Entérologie [CHRU de Tours]
49 Service d'hépato-gastro-entérologie [Hôpital Saint-Louis, APHP]
50 Service de Gastro-entérologie et hépatologie [AP-HP Hôpital Cochin]
51 Service d’hépato-gastro-entérologie [CH Le Raincy-Montfermeil]
52 Observatory on Efficacy and of Vedolizumab in Patients With Inflammatory Bowel Disease Study Group
53 GETAID - Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif
54 Hôpital Edouard Herriot [CHU - HCL]
55 Stress et Interactions neuro-digestives
56 Centre Hospitalier de Meaux

Background & aims - Phase 3 trials have shown the efficacy of vedolizumab, which binds to integrin α4β7, in patients with Crohn's disease (CD) or ulcerative colitis (UC). We investigated the effectiveness and safety of vedolizumab in patients who failed anti-tumor necrosis factor therapy. Methods - From June through December 2014, there were 173 patients with CD and 121 patients with UC who were included in a multicenter nominative compassionate early access program granted by French regulatory agencies. This program provided patients with access to vedolizumab before it was authorized for marketing. Vedolizumab (300 mg) was administered intravenously at weeks 0, 2, and 6, and then every 8 weeks. Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. We report results obtained after the 14-week induction phase. Results - Among the 294 patients treated with vedolizumab (mean age, 39.5 ± 14.0 y; mean disease duration, 10.8 ± 7.6 y; concomitant steroids, 44% of cases), 276 completed the induction period, however, 18 discontinued vedolizumab because of a lack of response (n = 14), infusion-related reaction (n = 2), or infections (n = 2). At week 14, 31% of patients with CD were in steroid-free clinical remission and 51% had a response; among patients with UC, 36% were in steroid-free clinical remission and 50% had a response. No deaths were reported. Severe adverse events occurred in 24 patients (8.2%), including 15 (5.1%) that led to vedolizumab discontinuation (1 case of pulmonary tuberculosis and 1 rectal adenocarcinoma). Conclusions - In a cohort of patients with CD or UC who failed previous anti-tumor necrosis factor therapy, approximately one third of patients achieved steroid-free clinical remission after 14 weeks of induction therapy with vedolizumab. This agent had an acceptable safety profile in these patients.

Keywords: drug; inhibitor; cell adhesion; IBD

Domains: Life Sciences [q-bio]

Aurelien Amiot, Jean-Charles Grimaud, Laurent Peyrin-Biroulet, Jérome Filippi, Benjamin Pariente, et al.. Effectiveness and Safety of Vedolizumab Induction Therapy for Patients with Inflammatory Bowel Disease. Clinical Gastroenterology and Hepatology, 2016, 14 (11), pp.1593-1601.e2. ⟨10.1016/j.cgh.2016.02.016⟩. ⟨hal-01278611⟩