1. Long-term effectiveness and safety of anti-TNF in pediatric-onset inflammatory bowel diseases: A population-based study.
- Author
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Fumery M, Dupont C, Ley D, Savoye G, Bertrand V, Guillon N, Wils P, Gower-Rousseau C, Sarter H, Turck D, and Leroyer A
- Subjects
- Adolescent, Child, Female, Humans, Young Adult, Adalimumab adverse effects, Infliximab therapeutic use, Retrospective Studies, Tumor Necrosis Factor Inhibitors therapeutic use, Tumor Necrosis Factor-alpha, Colitis, Ulcerative drug therapy, Crohn Disease drug therapy, Inflammatory Bowel Diseases drug therapy
- Abstract
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., Competing Interests: Conflict of interest MF has received lecture/consultant fees from Abbvie, Ferring, Tillots, MSD, Biogen, Amgen, Fresenius, Hospira, Sandoz, Pfizer, Celgene, Gilead, Boehringer, Galapagos, Janssen and Takeda. CD has received consultant fees from Abbvie. PW: none DL has received lecture/consultant fees from Abbvie and Sandoz. The other authors state that they have no competing interests regarding this work to disclose., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2024
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