Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada.
Alimentiv, Inc., London, ON, Canada.
BioDrugs. 2020 Dec;34(6):713-721. doi: 10.1007/s40259-020-00451-w.
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.
炎症性肠病（IBD）是一种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的复杂相互作用引起的，导致异常的免疫反应，从而引发肠道炎症。许多驱动炎症的途径已经被描述，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 的发病机制中起关键作用。靶向 IL-23 是治疗 IBD 的有效方法。乌司奴单抗，一种针对 IL-12/23 共享 p40 亚单位的单克隆抗体，已被批准用于治疗中重度 CD 和 UC。针对特定的 IL-23p19 拮抗剂正在开发中，米利珠单抗和 risankizumab 的 II 期临床试验的有前途结果强调了这类治疗的潜力。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。
