Efficacy and safety of combination targeted therapies in immune-mediated inflammatory disease: the COMBIO study

Lucas Guillo (1, 2) , Benoit Flachaire (1, 2) , Jérôme Avouac (3) , Catherine Dong (4) , Maria Nachury (5) , Guillaume Bouguen (6, 7, 8) , Anthony Buisson (9) , Ludovic Caillo (10) , Mathurin Fumery (11, 12) , Cyrielle Gilletta (13) , Xavier Hébuterne (14) , Pierre Lafforgue (1, 2) , David Laharie (15) , Emmanuel Mahé (16) , Hubert Marotte (17) , Stéphane Nancey (18) , Sébastien Ottaviani (19) , Jean-Hugues Salmon (20) , Guillaume Savoye (21, 22, 23, 24) , Mélanie Serrero (1) , Mathieu Uzzan (25) , Manuelle Viguier (26) , Christophe Richez (27) , Laurent Peyrin‐biroulet (28, 29) , Philipe Seksik (30) , Thao Pham (1, 2) , Philippe Ah-Soune , Nadia Arab , Laurent Beaugerie , Loïs Bolko , Joelle Bonnet , Yoram Bouhnik , Anne Bourrier , Franck Brazier (11) , Franck Carbonnel , Maeva Charkaoui , Isabelle Charlot-Lambrecht , Antoine Chupin , Alice Combier , Marion Couderc , Fabienne Coury-Lucas , Ariadne Desjeux , Nicolas Duveau , Anne Grasland , Jean-Charles Grimaud , Xavier Guennoc , Cécilia Landman , Isabelle Nion-Larmurier , Catherien Leberre , Romain Leenhardt , Aude Le Goffic , Henri Montaudie , Jacques Morel , Thierry Passeron , Jeanne-Marie Perotin Collard , Elodie Poisnel , Vincent Pradel , Martin Soubrier , Harry Sokol , Eric Toussirot , Caroline Trang , My-Linh Trans Minh , Sophie Trijau , Frank Verhoeven , Stéphanie Viennot , Daniel Wendling

1 Hôpital Nord [CHU - APHM]
2 APHM - Assistance Publique - Hôpitaux de Marseille
3 Service de rhumatologie [CHU Cochin]
4 Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre]
5 INFINITE (Ex-Liric) - Institute for Translational Research in Inflammation - U 1286
6 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
7 CIC - Centre d'Investigation Clinique [Rennes]
8 NuMeCan - Nutrition, Métabolismes et Cancer
9 3IHP - Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand]
10 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
11 CHU Amiens-Picardie
12 PERITOX - Périnatalité et Risques Toxiques - UMR INERIS_I 1
13 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
14 CHU Nice - Centre Hospitalier Universitaire de Nice
15 Hôpital Haut-Lévêque [CHU Bordeaux]
16 Centre Hospitalier Victor Dupouy
17 LBTO - Biologie Intégrative du Tissu Osseux
18 CIRI - Centre International de Recherche en Infectiologie
19 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
20 VIEFRA - EA 3797 - Vieillissement, Fragilité
21 ADEN - Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau
22 IRIB - Institute for Research and Innovation in Biomedicine
23 UNIROUEN - Université de Rouen Normandie
24 Service d'Hépato-Gastroentérologie [CHU Rouen]
25 Service de Gastroentérologie [Hôpital Beaujon]
26 Hôpital universitaire Robert Debré [Reims]
27 ImmunoConcept - Immunology from Concept and Experiments to Translation
28 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
29 Service d'Hépato-gastro-entérologie [CHRU Nancy]
30 CRSA - Centre de Recherche Saint-Antoine

BACKGROUND: Use of a combination of targeted therapies (COMBIO) in patients with refractory/overlapping immune-mediated inflammatory diseases (IMIDs) has increased, but reported data remain scarce. We aimed to assess effectiveness and safety of COMBIO in patients with IMIDs. METHODS: We conducted a French ambispective multicenter cohort study from September 2020 to May 2021, including adults' patients with 1 or 2 IMIDs and treated at least 3-month with COMBIO. RESULTS: Overall, 143 patients were included. The most common IMIDs were Crohn's disease (63.6%), axial spondyloarthritis (37.7%), and ulcerative colitis (14%). Half of patients had only one IMID, of which 60% were Crohn's disease. Mean duration of COMBIO was 274.5±59.3 weeks, and COMBIO persistence at 104 weeks was estimated at 64.1%. The most frequent COMBIOs combined anti-TNF agents with vedolizumab (30%) or ustekinumab (28.7%). Overall, 50% of patients achieved significant and 27% mild-to-moderate improvement in patient-reported outcomes. Extended duration of COMBIO (aOR=1.09; 95% CI: 1.03-1.14; p=0.002) and diagnoses of two IMIDs (aOR=3.46; 95%CI: 1.29-9.26; p=0.013) were associated with significant improvement in patient-reported outcomes. Incidence of serious infection during COMBIO was 4.51 per 100 person-years (95% CI 2.20-8.27) and 5 COMBIOs were discontinued due to adverse events. CONCLUSIONS: COMBIO can be effective and safe in patients with refractory/overlapping IMIDs.

Mots clés: Combination therapy; Immune-mediated inflammatory diseases; Molecular targeted therapy

Domaines: Sciences du Vivant [q-bio]; Hépatologie et Gastroentérologie

Lucas Guillo, Benoit Flachaire, Jérôme Avouac, Catherine Dong, Maria Nachury, et al.. Efficacy and safety of combination targeted therapies in immune-mediated inflammatory disease: the COMBIO study. Digestive and Liver Disease, 2023, 55 (1), pp.61-68. ⟨10.1016/j.dld.2022.07.012⟩. ⟨hal-04167918⟩