使用risankizumab靶向IL23p19治疗中度至重度活动性克罗恩病

Christopher Ma
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引用次数: 0

摘要

通过抑制白细胞介素(IL)-23靶向th17介导的炎症通路已成为炎症性肠病患者的重要治疗机制。Ustekinumab是一种阻断IL-12和IL-23的单克隆抗体,是加拿大卫生部批准的第一种具有这种作用机制的药物,最初于2016年用于克罗恩病(CD),随后于2020年用于溃疡性结肠炎(UC)。在过去的十年中,选择性阻断IL-23作为致病性Th17炎症细胞的关键激活剂越来越受到关注。针对IL-23独特的p19亚基(il - 23p19拮抗剂)的几种单克隆抗体已被开发用于银屑病和银屑病关节炎,与针对IL-12/23相比,IL-23特异性阻断的疗效显著提高。首个IL23p19拮抗剂risankizumab最近在加拿大被批准用于治疗中度至重度活动性CD。在这里,我们描述了risankizumab的作用机制以及它与ustekinumab的区别;回顾关键的临床试验数据,证明利桑单抗能够在生物治疗naïve和暴露患者中达到相关的临床和内窥镜终点;并总结关键的安全性数据,这些数据有助于决定这种新疗法的收益-风险概况。
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Targeting IL23p19 using risankizumab for the management of moderate-to-severely active Crohn's disease
Targeting Th17-mediated inflammatory pathways through inhibition of interleukin (IL)-23 has emerged as an important therapeutic mechanism for patients with inflammatory bowel disease. Ustekinumab, a monoclonal antibody blocking both IL-12 and IL-23, was the first agent approved by Health Canada with this mechanism of action, initially for Crohn’s disease (CD) in 2016 and subsequently for ulcerative colitis (UC) in 2020. Over the past decade, there has been increasing attention focused on selectively blocking IL-23, as the key activator of pathogenic Th17 inflammatory cells. Several monoclonal antibodies that target the unique p19 subunit of IL-23 (IL23p19 antagonists) have been developed for psoriasis and psoriatic arthritis, where IL-23 specific blockade results in substantially greater efficacy compared to targeting IL-12/23. The first IL23p19 antagonist, risankizumab, has recently been approved in Canada for the treatment of moderate-to-severely active CD. Here, we describe the mechanism of action of risankizumab and how it differentiates from ustekinumab; review the pivotal clinical trial data that demonstrates the ability of risankizumab to achieve relevant clinical and endoscopic endpoints in both biologic treatment naïve and exposed patients; and summarize key safety data that helps inform decisions about the benefit-risk profile of this novel therapy.
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