Long-term effectiveness and safety of anti-TNF in pediatric-onset inflammatory bowel diseases: A population-based study

Mathurin Fumery (1, 2) , Claire Dupont (3, 4) , Delphine Ley (5) , Guillaume Savoye (6, 7, 8, 9) , Valérie Bertrand (6, 7, 10) , Nathalie Guillon (11, 5) , Pauline Wils (12) , Corinne Gower-Rousseau (5) , Helene Sarter (5) , Dominique Turck (5, 12) , Ariane Leroyer (12, 5)

1 PERITOX - Périnatalité et Risques Toxiques - UMR INERIS_I 1
2 CHU Amiens-Picardie
3 LTSI - Laboratoire Traitement du Signal et de l'Image
4 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
5 INFINITE (Ex-Liric) - Institute for Translational Research in Inflammation - U 1286
6 ADEN - Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau
7 IRIB - Institute for Research and Innovation in Biomedicine
8 UNIROUEN UFR Santé - UNIROUEN - UFR Santé
9 Service d'Hépato-Gastroentérologie [CHU Rouen]
10 GHH - Groupe Hospitalier du Havre Hôpital Jacques Monod (MONTIVILLIERS)
11 Service d'Epidémiologie et de Santé Publique [Lille]
12 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]

Background: Anti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD. Methods: All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model. Results: Among a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1-20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0-59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02-2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30-4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15-0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment. Conclusion: In a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.

Mots clés: Crohn's disease; Loss of response; Primary non-response; Ulcerative colitis; anti-TNF

Domaines: Médecine humaine et pathologie

Mathurin Fumery, Claire Dupont, Delphine Ley, Guillaume Savoye, Valérie Bertrand, et al.. Long-term effectiveness and safety of anti-TNF in pediatric-onset inflammatory bowel diseases: A population-based study. Digestive and Liver Disease, 2023, ⟨10.1016/j.dld.2023.04.017⟩. ⟨hal-04088937⟩