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新型白细胞介素-23拮抗剂在克罗恩病中的应用。

New Interleukin-23 Antagonists' Use in Crohn's Disease.

作者信息

Biskup Laura, Semeradt Jan, Rogowska Jagoda, Chort Wiktoria, Durko Łukasz, Małecka-Wojciesko Ewa

机构信息

Department of Digestive Tract Diseases, Medical University of Lodz, 90-419 Lodz, Poland.

出版信息

Pharmaceuticals (Basel). 2025 Mar 22;18(4):447. doi: 10.3390/ph18040447.

DOI:10.3390/ph18040447
PMID:40283885
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12030181/
Abstract

Crohn's disease (CD) is a chronic inflammatory condition of the digestive tract, driven by an imbalance in immune system regulation, where proinflammatory interleukin-23 (IL-23) plays an essential role. Selective new IL-23 inhibitors, including risankizumab, guselkumab, and mirikizumab, block the IL-23p19 subunit to inhibit the Il-23 action and alleviate inflammation in CD. This review explores the effectiveness, safety, and therapeutic potential of anti-IL-23 treatment in CD management. Risankizumab, guselkumab, and mirikizumab demonstrated considerable effectiveness in inducing clinical remission and promoting endoscopic healing in patients with moderately to severely active CD, including those refractory to anti-TNF therapies. Risankizumab showed favorable results in pivotal trials like ADVANCE, MOTIVATE, and FORTIFY, achieving remission rates of up to 45% and sustained inflammatory biomarkers normalization. Guselkumab and mirikizumab similarly demonstrated substantial efficacy in the induction and maintenance phases, with promising long-term results. The safety profiles of IL-23 inhibitors were favorable, with low rates of serious adverse events, including infections and malignancies. Selective new IL-23 inhibitors represent a targeted and effective therapeutic class for moderately to severely active CD, offering high clinical and endoscopic remission rates, and favorable safety outcomes. Continued research, particularly on long-term efficacy and the selection of patients based on inflammatory biomarkers, will help optimize their role in personalized treatment strategies for refractory CD.

摘要

克罗恩病(CD)是一种消化道慢性炎症性疾病,由免疫系统调节失衡所致,其中促炎白细胞介素-23(IL-23)起关键作用。选择性新型IL-23抑制剂,包括瑞莎珠单抗、古塞库单抗和mirikizumab,可阻断IL-23p19亚基以抑制IL-23的作用,并减轻CD中的炎症。本综述探讨了抗IL-23治疗在CD管理中的有效性、安全性及治疗潜力。瑞莎珠单抗、古塞库单抗和mirikizumab在诱导中度至重度活动性CD患者临床缓解及促进内镜愈合方面显示出显著疗效,包括那些对抗肿瘤坏死因子(TNF)治疗难治的患者。瑞莎珠单抗在ADVANCE、MOTIVATE和FORTIFY等关键试验中显示出良好结果,缓解率高达45%,并使炎症生物标志物持续恢复正常。古塞库单抗和mirikizumab在诱导期和维持期同样显示出显著疗效,长期结果令人期待。IL-23抑制剂的安全性良好,严重不良事件发生率低,包括感染和恶性肿瘤。选择性新型IL-23抑制剂是治疗中度至重度活动性CD的一种靶向且有效的治疗类别,具有较高的临床和内镜缓解率以及良好的安全性结果。持续的研究,特别是关于长期疗效以及基于炎症生物标志物选择患者的研究,将有助于优化它们在难治性CD个性化治疗策略中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/317a/12030181/ffa87b5b02ca/pharmaceuticals-18-00447-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/317a/12030181/ffa87b5b02ca/pharmaceuticals-18-00447-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/317a/12030181/ffa87b5b02ca/pharmaceuticals-18-00447-g001.jpg

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本文引用的文献

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Gastro Hep Adv. 2024 Dec 24;4(4):100603. doi: 10.1016/j.gastha.2024.100603. eCollection 2025.
2
Extended Risankizumab Treatment in Patients With Crohn's Disease Who Did Not Achieve Clinical Response to Induction Treatment.对诱导治疗未达到临床反应的克罗恩病患者进行的司库奇尤单抗延长治疗
Clin Gastroenterol Hepatol. 2025 Feb 3. doi: 10.1016/j.cgh.2024.12.023.
3
Unraveling the role of autophagy regulation in Crohn's disease: from genetic mechanisms to potential therapeutics.
解析自噬调节在克罗恩病中的作用:从遗传机制到潜在治疗方法
Adv Biotechnol (Singap). 2024 Mar 21;2(2):14. doi: 10.1007/s44307-024-00021-z.
4
Early Endoscopic Outcomes After Risankizumab Are Associated With Fewer Hospitalizations and Surgeries in Crohn's Disease.司库奇尤单抗治疗后的早期内镜结果与克罗恩病患者较少的住院和手术相关。
Gastro Hep Adv. 2024 Sep 5;4(1):100544. doi: 10.1016/j.gastha.2024.08.022. eCollection 2025.
5
Long-Term Effectiveness and Safety of Ustekinumab in Crohn's Disease: Results from a Large Real-Life Cohort Study.优特克单抗治疗克罗恩病的长期有效性和安全性:一项大型真实世界队列研究的结果
J Clin Med. 2024 Nov 27;13(23):7192. doi: 10.3390/jcm13237192.
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