Department of Gastroenterology, St Thomas' Hospital, London, UK.
School of Immunology and Microbial Sciences, King's College London, London, UK.
Expert Opin Biol Ther. 2024 Nov;24(11):1199-1206. doi: 10.1080/14712598.2024.2412650. Epub 2024 Oct 16.
Treatment of ulcerative colitis (UC) aims to reduce symptoms and complications by decreasing intestinal inflammation. A proportion of patients do not respond to, do not tolerate, or are inappropriate candidates for current therapies. Interleukin (IL)-23 is a therapeutic target and mirikizumabis the first p19-targeted IL-23 antibody approved for the treatment of moderately to severely active UC.
This review summarizes the pro-inflammatory effects of IL-23 and outlines the pharmacokinetics of mirikizumab. It provides a synopsis of the available phase II and phase III evidence for the efficacy and safety of mirikizumab in UC.
The mirikizumab clinical development program demonstrated its superiority over placebo and its favorable safety profile in the treatment of UC. Its positioning in therapeutic algorithms remains to be fully understood but mirikizumab has proven efficacy in both advanced therapy (AT)-naïve and AT-experienced patients. The inclusion in the license of extended induction for non-responders as well as rescue intravenous dosing allows for flexibility in patient with limited primary response and secondary loss of response.
溃疡性结肠炎（UC）的治疗目的是通过减少肠道炎症来减轻症状和并发症。一部分患者对当前的治疗方法无反应、不耐受或不适合。白细胞介素（IL）-23 是一个治疗靶点，米利珠单抗是首个获批用于治疗中重度活动性 UC 的靶向 p19 的 IL-23 抗体。
本文综述了 IL-23 的促炎作用，并概述了米利珠单抗的药代动力学。本文总结了米利珠单抗治疗 UC 的 II 期和 III 期有效性和安全性的现有证据。
米利珠单抗的临床开发项目表明，它在治疗 UC 方面优于安慰剂，且具有良好的安全性。其在治疗方案中的定位仍有待充分了解，但米利珠单抗已被证明在初治和治疗后复发的患者中均具有疗效。在许可证中纳入非应答者的扩展诱导以及抢救性静脉注射剂量，为应答有限和二次应答丧失的患者提供了灵活性。
