Clinical Trials of IL-12/IL-23 Inhibitors in Inflammatory Bowel Disease
Clinical Trials of IL-12/IL-23 Inhibitors in Inflammatory Bowel Disease
复制标题
IL-12/IL-23抑制剂治疗炎症性肠病的临床研究
DOI：
10.1007/s40259-020-00451-w
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发表时间：
2020-10-26
期刊：
影响因子：
6.8
通讯作者：
Jairath, Vipul
中科院分区：
文献类型：
--
作者：
Almradi, Ahmed;Hanzel, Jurij;Jairath, Vipul
炎症性肠病（IBDs）是慢性免疫介导的炎症性疾病，包括溃疡性结肠炎（UC）和克罗恩病（CD）。IBD是由环境、微生物和遗传因素之间复杂的相互作用引起的，导致肠道炎症的异常免疫反应。已经描述了许多驱动炎症的途径，并且不同的途径可能在个体患者中占主导地位。白细胞介素(IL)-23途径通过促进病理性Th17反应在IBD发病机制中起关键作用。靶向IL-23治疗IBD是有效的。Ustekinumab是一种靶向IL-12/23共享p40亚基的单克隆抗体，已被批准用于治疗中至重度CD和UC。特异性IL-23p19拮抗剂正在开发中，mirikizumab和risankizumab的II期试验结果表明，这类治疗的潜力很大。在这篇综述中，我们总结了不同IL-23拮抗剂治疗IBD的作用机制和临床试验证据，这些证据支持不同IL-23拮抗剂的有效性和安全性。
The inflammatory bowel diseases (IBDs) are chronic immune-mediated inflammatory disorders, including ulcerative colitis (UC) and Crohn's disease (CD). IBD results from a complex interplay between environmental, microbial, and genetic factors to create an abnormal immunological response leading to intestinal inflammation. Many pathways driving inflammation have been described, and different pathways may predominate in an individual patient. The interleukin (IL)-23 pathway plays a key role in IBD pathogenesis through promoting a pathological Th17 response. Targeting IL-23 is effective in the treatment of IBD. Ustekinumab, a monoclonal antibody targeting the shared p40 subunit of IL-12/23, is approved for treatment of moderate-to-severe CD and UC. Specific IL-23p19 antagonists are in development and promising results from phase II trials of mirikizumab and risankizumab underscore the potential for this class of treatment. In this review, we summarize the mechanisms of action and the evidence from clinical trials supporting the efficacy and safety of different IL-23 antagonists for IBD.