A clinical decision support tool may help to optimise vedolizumab therapy in Crohn's disease

Parambir S. Dulai , Aurélien Amiot (1) , Laurent Peyrin-Biroulet (2, 3) , Vipul Jairaith (4) , Mélanie Serrero (1) , Jérome Filippi (5) , Siddharth Singh (6) , Benjamin Pariente (1) , Edward V. Loftus (7) , Xavier Roblin (8) , Sunanda Kane , Anthony Buisson (9) , Corey A. Siegel (10) , Yoram Bouhnik (11) , William J. Sandborn (6, 7) , Karen Lasch , Maria Rosario (12) , Brian G. Feagan (13) , Daniela Bojic , Caroline Trang-Poisson (14, 15, 16) , Bo Shen (17) , Romain Altwegg (1) , Bruce E. Sands , Jean-Frederic Colombel (18) , Franck Carbonnel (19) , Gursimran Kochhar , Joseph Meserve , Maria Barsky , Brigid S. Boland , Charlotte Gagniere (20) , Marc-André Bigard (3) , Camille Zallot (3, 2) , Jean-Charles Grimaud (21) , Xavier Hebuterne (5, 22) , Maria Nachury (23) , Pierre Desreumaux (23) , Emilie del Tedesco (24) , Gilles Bommelaer (9) , Jenna L. Koliani-Pace , Carmen Stefanescu (1) , Arnaud Boureille (14) , Robert Hirten , Ryan Ungaro , Thibaud Vaysse (25) , Matthew Bohm , Sashidhar Varma , Monika Fischer (26) , David Hudesman , Shannon Chang , Anne Bourrier (27) , Philippe Seksik (28, 27) , Laurent Beaugerie (29) , Jacques Cosnes (27) , Harry Sokol (28) , Cécilia Landman (27) , Dana Lukin , Aaron Weiss , Philippe Marteau (30) , Xavier Dray (31, 32, 33) , Stephane Nancey (1) , Gilles Boschetti (34) , David Laharie (35, 36) , Florian Poullenot (36) , Matthieu Allez (37) , Jean-Marc Gornet (37) , Clautilde Baudry (38) , Guillaume Savoye (39, 40, 41, 42) , Jacques Moreau (43) , Lucine Vuitton (1) , Stéphane Koch (44) , Stéphanie Viennot (1) , Alexandre Aubourg (45) , Laurence Picon (46) , Anne-Laure Pelletier (47) , Gaelle Sickersen (48) , Guillaume Bouguen (1) , Vered Abitbol (49, 50) , Stanislas Chaussade (49, 50) , Stéphane Nahon (51) , Mathurin Fumery (1, 52, 53) , Betsy Winkfield (54, 1) , Hedia Brixi-Benmansour (1) , Rodica Gincul (55) , Jean-Christophe Barberis (54) , Bruno Bonaz (56) , Christophe Michiels (57) , Frank Zerbib (35) , Marie Bourrier De Beauregard , Christophe Locher (58) , Sophie Davin-Couve (54) , Armelle Poirette (54) , Laurence Guillem (54) , Monica Stetiu-Mocanu (54) , Beau Philippe , Sylvain Beorchia (54) , Jawad Al Qaddi (54) , Arun Swaminath , Getaid Observ-Ibd , Victory Cohorts Collaboration

1 GETAID - Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif
2 Service d'Hépato-gastro-entérologie [CHRU Nancy]
3 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
4 UWO - University of Western Ontario
5 CHU Nice - Centre Hospitalier Universitaire de Nice
6 UC San Diego - University of California [San Diego]
7 Mayo Clinic [Rochester]
8 CHU de Saint-Etienne - Centre Hospitalier Universitaire de Saint-Etienne
9 M2iSH - Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte
10 Dartmouth Hitchcock Medical Center
11 Service de Gastroentérologie [Hôpital Beaujon]
12 CICECO Department of chemistry and physics
13 Robarts Research Institute [Canada]
14 CHU Nantes - Centre hospitalier universitaire de Nantes
15 Institut des Maladies de l'Appareil Digestif
16 CIC Nantes - Centre d’Investigation Clinique de Nantes
17 CUIMC - Columbia University Irving Medical Center
18 MSSM - Icahn School of Medicine at Mount Sinai [New York]
19 AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
20 EC2M3 - Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375)
21 APHM - Assistance Publique - Hôpitaux de Marseille
22 UCA - Université Côte d'Azur
23 Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille]
24 Service de gastroentérologie [CHU Saint-Etienne]
25 Service de neurologie [Le Kremlin Bicêtre]
26 IUPUI - Indiana University - Purdue University Indianapolis
27 Service de Gastroentérologie et nutrition [CHU Saint-Antoine]
28 CRSA - Centre de Recherche Saint-Antoine
29 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
30 CHU Saint-Antoine [AP-HP]
31 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
32 ETIS - UMR 8051 - Equipes Traitement de l'Information et Systèmes
33 SU - Sorbonne Université
34 APY - Autophagie infection et immunité - Autophagy Infection Immunity
35 CHU Bordeaux [Bordeaux]
36 Hôpital Haut-Lévêque [CHU Bordeaux]
37 AP-HP - Hopital Saint-Louis [AP-HP]
38 Service d'Endocrinologie, Diabétologie, Maladies Métaboliques, Hôpital Avicenne
39 ADEN - Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau
40 IRIB - Institute for Research and Innovation in Biomedicine
41 Service d'Hépato-Gastroentérologie [CHU Rouen]
42 UNIROUEN UFR Santé - UNIROUEN - UFR Santé
43 CHU Toulouse [Toulouse]
44 Service de Gastro-Entérologie [CHRU Besançon]
45 GICC EA 7501 - Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...]
46 Hépato-Gastro-Onco-Entérologie [CHRU de Tours]
47 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
48 Service d'hépato-gastro-entérologie [Hôpital Saint-Louis, APHP]
49 Hôpital Cochin [AP-HP]
50 USPC - Université Sorbonne Paris Cité
51 Groupe Hospitalier Intercommunal Le Raincy-Montfermeil
52 PERITOX - Périnatalité et Risques Toxiques - UMR INERIS_I 1
53 CHU Amiens-Picardie
54 Observatory on Efficacy and of Vedolizumab in Patients With Inflammatory Bowel Disease Study Group
55 Hôpital Edouard Herriot [CHU - HCL]
56 CHU - Centre Hospitalier Universitaire [Grenoble]
57 Service d'Hépato-Gastro-Entérologie (CHU de Dijon)
58 GHEF - Grand Hôpital de l'Est Francilien

Background A clinical decision support tool (CDST) has been validated for predicting treatment effectiveness of vedolizumab (VDZ) in Crohn's disease. Aim To assess the utility of this CDST for predicting exposure-efficacy and disease outcomes. Methods Using data from three independent datasets (GEMINI, GETAID and VICTORY), we assessed clinical remission rates and measured VDZ exposure, rapidity of onset of action, response to dose optimisation and progression to surgery by CDST-defined response groups (low, intermediate and high). Results A linear relationship existed between CDST-defined groups, measured VDZ exposure, rapidity of onset of action and efficacy in GEMINI through week 52 (P < 0.001 at all time points across three CDST-defined groups). In GETAID, CDST predicted differences in clinical remission at week 14 (AUC = 0.68) and rapidity of onset of action (P = 0.04) between probability groups. The high-probability patients did not benefit from shortening of infusion intervals, and differences in onset of action between the high-intermediate and low-probability groups within GETAID were no longer significant when including low-probability patients who received a week 10 infusion. CDST predicted a twofold increase in surgery risk over 12 months of VDZ therapy among low- to intermediate-probability vs high-probability patients (adjusted HR 2.06, 95% CI 1.33-3.21). Conclusions We further extended the clinical utility of a previously validated VDZ CDST, which accurately predicts at baseline exposure-efficacy relationships and rapidity of onset of action and could be used to help identify patients who would most benefit from interval shortening and those most likely to require surgery while on active therapy.

Domaines: Sciences du Vivant [q-bio]

Parambir S. Dulai, Aurélien Amiot, Laurent Peyrin-Biroulet, Vipul Jairaith, Mélanie Serrero, et al.. A clinical decision support tool may help to optimise vedolizumab therapy in Crohn's disease. Alimentary Pharmacology and Therapeutics, 2020, 51 (5), pp.553-564. ⟨10.1111/apt.15609⟩. ⟨hal-03552288⟩