Targeting the Interleukin 23 Pathway in Inflammatory Bowel Disease.

IF 25.7 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Gastroenterology Pub Date : 2025-01-01 Epub Date: 2024-06-28 DOI:10.1053/j.gastro.2024.05.036

Arno R Bourgonje, Ryan C Ungaro, Saurabh Mehandru, Jean-Frédéric Colombel

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Abstract

Interleukin (IL) 23, a member of the IL12 family of cytokines, maintains intestinal homeostasis, but is also implicated in the pathogenesis of inflammatory bowel diseases (IBDs). IL23 is a heterodimer composed of disulfide-linked p19 and p40 subunits. Humanized monoclonal antibodies selectively targeting the p19 subunit of IL23 are poised to become prominent drugs in IBDs. In this review, we discuss the pharmacodynamic and pharmacokinetic properties of the currently available IL23p19 inhibitors and discuss the mechanistic underpinnings of their therapeutic effects, including the mechanism of action, epitope affinity, potency, and downstream signaling. Furthermore, we address available data on the efficacy, safety, and tolerability of IL23p19 inhibitors in the treatment of IBDs and discuss important studies performed in other immune-mediated inflammatory diseases. Finally, we evaluate the potential for combining classes of biological therapies and provide future directions on the development of precision medicine-guided positioning of IL23p19 inhibitors in IBD.

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靶向炎症性肠病中的 IL-23 通路

白细胞介素-23（IL-23）是 IL-12 细胞因子家族的成员，它能维持肠道平衡，但也与炎症性肠病（IBD）的发病机制有关。IL-23 受体（IL-23R）是由二硫键连接的 p19 和 p23 亚基组成的异二聚体。选择性靶向 IL-23 的 p19 亚基的人源化单克隆抗体有望成为治疗 IBD 的主要药物。在这篇综述中，我们讨论了目前可用的 IL-23p19 抑制剂的药效学和药代动力学特性，并讨论了其治疗效果的机理基础，包括作用机制、表位亲和力、效力和下游信号传导。此外，我们还讨论了有关 IL-23 特异性 p19 抑制剂治疗 IBD 的疗效、安全性和耐受性的现有数据，并讨论了在其他免疫介导的炎症性疾病中进行的重要研究。最后，我们评估了联合生物疗法的潜力，并提供了以精准医疗为指导定位 IL-23p19 抑制剂治疗 IBD 的未来发展方向。

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来源期刊

Gastroenterology 医学-胃肠肝病学

CiteScore

45.60

自引率

2.40%

发文量

4366

审稿时长

26 days

期刊介绍： Gastroenterology is the most prominent journal in the field of gastrointestinal disease. It is the flagship journal of the American Gastroenterological Association and delivers authoritative coverage of clinical, translational, and basic studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. Some regular features of Gastroenterology include original research studies by leading authorities, comprehensive reviews and perspectives on important topics in adult and pediatric gastroenterology and hepatology. The journal also includes features such as editorials, correspondence, and commentaries, as well as special sections like "Mentoring, Education and Training Corner," "Diversity, Equity and Inclusion in GI," "Gastro Digest," "Gastro Curbside Consult," and "Gastro Grand Rounds." Gastroenterology also provides digital media materials such as videos and "GI Rapid Reel" animations. It is abstracted and indexed in various databases including Scopus, Biological Abstracts, Current Contents, Embase, Nutrition Abstracts, Chemical Abstracts, Current Awareness in Biological Sciences, PubMed/Medline, and the Science Citation Index.

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