Solitano Virginia, Estevinho Maria Manuela, Ungaro Federica, Magro Fernando, Danese Silvio, Jairath Vipul
Division of Gastroenterology, Department of Medicine, Western University Schulich School of Medicine, London, ON, Canada.
Division of Gastroenterology and Gastrointestinal Endoscopy, IRCCS Ospedale San Raffaele, Università Vita-Salute San Raffaele, Milan, Italy.
BioDrugs. 2025 Mar;39(2):171-183. doi: 10.1007/s40259-025-00706-4. Epub 2025 Feb 5.
Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), remains challenging to manage, with a substantial proportion of patients not responding to conventional therapies or developing complications. The tumor necrosis factor (TNF) superfamily member TL1A has emerged as an important player in the pathogenesis of IBD, influencing pathways of inflammation and fibrosis. This leading article reviews the role of TL1A in IBD, evaluates the efficacy of anti-TL1A therapies in clinical trials, and discusses future directions for research and treatment. TL1A is implicated in IBD through its interaction with death domain receptor 3 (DR3), promoting T-cell activation and contributing to both inflammatory responses and fibrotic changes. Phase 2 clinical trials of anti-TL1A agents have demonstrated promising results, showing improvements in endoscopic and histologic outcomes for both UC and CD. Phase 2 and 3 clinical trials are ongoing, which are expected to provide further clarity on the efficacy and safety of TL1A-targeting agents in treating IBD.
炎症性肠病（IBD），包括克罗恩病（CD）和溃疡性结肠炎（UC），其治疗仍然具有挑战性，相当一部分患者对传统疗法无反应或出现并发症。肿瘤坏死因子（TNF）超家族成员TL1A已成为IBD发病机制中的一个重要因素，影响炎症和纤维化途径。这篇前沿文章综述了TL1A在IBD中的作用，评估了抗TL1A疗法在临床试验中的疗效，并讨论了未来的研究和治疗方向。TL1A通过与死亡结构域受体3（DR3）相互作用而与IBD相关，促进T细胞活化，并导致炎症反应和纤维化改变。抗TL1A药物的2期临床试验已显示出有前景的结果，在UC和CD的内镜和组织学结果方面均有改善。2期和3期临床试验正在进行中，预计将进一步明确靶向TL1A的药物在治疗IBD方面的疗效和安全性。
