Efficacy and Safety of Tumor Necrosis Factor Antagonists in Treatment of Internal Fistulizing Crohn's Disease

Guillaume Bouguen (1, 2) , Audrey Huguet (3) , Aurelien Amiot (4) , Stéphanie Viennot (5) , Franck Cholet (6) , Maria Nachury (3) , Mathurin Flamant (7) , Jean-Marie Reimund (8) , Véronique Desfourneaux (3) , Arnaud Boureille (7) , Laurent Siproudhis (1, 2)

1 NuMeCan - Nutrition, Métabolismes et Cancer
2 CIC - Centre d'Investigation Clinique [Rennes]
3 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
4 Service d'hépato-gastro-entérologie [APHP Henri Mondor]
5 Hôpital Côte de Nacre [CHU Caen]
6 CHU-Brest-Hemato - CHRU Brest - Service d'Hématologie
7 CHU Nantes - Centre Hospitalier Universitaire de Nantes
8 Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques

Background & aims - Few data are available on the effects of tumor necrosis factor (TNF) antagonist therapy for patients with internal fistulizing Crohn's disease (CD) and there is debate regarding the risk of abscess. We aimed to assess the long-term efficacy and safety of anti-TNF therapy for patients with internal fistulas. Methods - We performed a retrospective study of data collected from the Groupe d'Etude Thérapeutique des Affections Inflammatoires Digestives trial, from January 1, 2000, through December 31, 2017. Our final analysis included 156 patients who began treatment with an anti-TNF agent for CD with internal fistula (83 men; median disease duration, 4.9 y). The primary end point was the onset of a major abdominal surgery. Secondary analysis included disappearance of the fistula tract during follow-up evaluation and safety. The Kaplan-Meier method was used for statistical analysis. Results - After a median follow-up period of 3.5 years, 68 patients (43.6%) underwent a major abdominal surgery. The cumulative probabilities for being surgery-free were 83%, 64%, and 51% at 1, 3, and 5 years, respectively. A concentration of C-reactive protein >18 mg/L, an albumin concentration <36 g/L, the presence of an abscess at the fistula diagnosis, and the presence of a stricture were associated independently with the need for surgery. The cumulative probabilities of fistula healing, based on imaging analyses, were 15.4%, 32.3%, and 43.9% at 1, 3, and 5 years, respectively. Thirty-two patients (20.5%) developed an intestinal abscess and 4 patients died from malignancies (3 intestinal adenocarcinomas). One patient died from septic shock 3 months after initiation of anti-TNF therapy. Conclusions - In a retrospective analysis of data from a large clinical trial, we found that anti-TNF therapy delays or prevents surgery for almost half of patients with CD and luminal fistulas. However, anti-TNF therapy might increase the risk for sepsis-related death or gastrointestinal malignancies.

Mots clés: prognostic factor; infliximab; GETAID; inflammatory bowel disease

Domaines: Hépatologie et Gastroentérologie; Immunothérapie

Guillaume Bouguen, Audrey Huguet, Aurelien Amiot, Stéphanie Viennot, Franck Cholet, et al.. Efficacy and Safety of Tumor Necrosis Factor Antagonists in Treatment of Internal Fistulizing Crohn's Disease. Clinical Gastroenterology and Hepatology, 2020, 18 (3), pp.628-636. ⟨10.1016/j.cgh.2019.05.027⟩. ⟨hal-02152872⟩