克罗恩病中IL-23抑制剂的鉴别

IF 13 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Drugs Pub Date : 2025-06-01 Epub Date: 2025-05-05 DOI:10.1007/s40265-025-02183-z
Olga Maria Nardone, Sudheer K Vuyyuru, Yuhong Yuan, Jurij Hanzel, Vipul Jairath
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引用次数: 0

摘要

白细胞介素-23 (IL-23)是IL-12细胞因子家族的一员,在肠道内稳态和炎症中起关键作用,并与炎症性肠病(IBD)的发病机制密切相关。针对IL-23的p19亚基的治疗最近扩大了IBD的治疗选择,证明了治疗中度至重度克罗恩病(CD)的有效性和安全性。因此,在这篇综述中,我们概述了靶向CD中IL-23途径的药物,并强调了特异性IL-23抑制剂的异同。此外,我们总结了关键的3期试验和头对头试验,重点是设计特征和解释。最后,我们讨论了选择性IL-23药物在CD治疗中的定位以及未满足临床需求的领域。然而,真实世界的数据将提供额外的比较有效性信息、疾病亚型数据以及对IL-23抑制的长期结果的见解。展望未来,正在进行的测试p19特异性选择性IL-23抑制剂的3期研究有望扩大复杂表型患者的治疗选择,包括那些有肠外表现(EIMs)、瘘管和狭窄的患者。分子和细胞表征的进步,包括预测性分子生物标志物的发展,可能有助于指导临床决策,实现更个性化的治疗方法。精准医学研究可能会进一步加深我们对IL-23分子生物学的理解,揭示这些药物如何在复杂的乳糜泻中起作用,并阐明它们与其他疗法的潜在互补或协同作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Differentiating IL-23 Inhibitors in Crohn's Disease.

Interleukin-23 (IL-23), a member of the IL-12 family of cytokines, plays a critical role in intestinal homeostasis and inflammation and is strongly implicated in the pathogenesis of inflammatory bowel disease (IBD). Therapies targeting the p19 subunit of IL-23 have recently expanded the therapeutic options for IBD demonstrating efficacy and safety for the treatment of moderate to severe Crohn's disease (CD). Thus, in this review, we provide an overview of agents targeting the IL-23 pathway in CD, highlighting similarities and differences of specific IL-23 inhibitors. Furthermore, we summarize key phase 3 trials and head-to-head trials, focusing on design features and interpretation. Finally, we discuss the positioning of selective IL-23 agents for CD treatment along with areas of unmet clinical needs. However, real-world data will offer additional comparative effectiveness information, data for disease subtypes, and insights into the long-term outcomes of IL-23 inhibition. Looking ahead, ongoing phase 3 studies testing p19-specific selective IL-23 inhibitors are expected to expand the therapeutic options for patients with complex phenotypes, including those with extraintestinal manifestations (EIMs), fistulas, and strictures. Advances in molecular and cellular characterization, including the development of predictive molecular biomarkers, may help guide clinical decision-making, enabling more personalized treatment approaches. Precision medicine studies may further enhance our understanding of the molecular biology of IL-23, shedding light on how these agents work in complex CD and clarify their potential complementary or synergistic effects with other therapies.

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来源期刊
Drugs
Drugs 医学-毒理学
CiteScore
22.70
自引率
0.90%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Drugs is a journal that aims to enhance pharmacotherapy by publishing review and original research articles on key aspects of clinical pharmacology and therapeutics. The journal includes: Leading/current opinion articles providing an overview of contentious or emerging issues. Definitive reviews of drugs and drug classes, and their place in disease management. Therapy in Practice articles including recommendations for specific clinical situations. High-quality, well designed, original clinical research. Adis Drug Evaluations reviewing the properties and place in therapy of both newer and established drugs. AdisInsight Reports summarising development at first global approval. Moreover, the journal offers additional digital features such as animated abstracts, video abstracts, instructional videos, and podcasts to increase visibility and educational value. Plain language summaries accompany articles to assist readers with some knowledge of the field in understanding important medical advances.
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