Faculty of Medicine, University of Ljubljana, Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Department of Gastroenterology and Hepatology, Amsterdam University Medical Centres, Academic Medical Centre, Amsterdam, The Netherlands.
Expert Rev Clin Immunol. 2022 May;18(5):513-524. doi: 10.1080/1744666X.2022.2069562. Epub 2022 May 1.
Despite advances in the medical management of ulcerative colitis (UC), a subgroup of patients does not respond to currently available therapies. A number of novel drugs are in late stages of clinical development or have recently received regulatory approval for UC.
This review focuses on three drug classes that have recently been approved or are awaiting approval for UC: antibodies against interleukin (IL)-23, sphingosine-1-phosphate receptor (S1PR) modulators, and selective inhibitors of Janus kinases (JAK). We provide an overview of their mechanism of action and summarize available evidence for their efficacy and safety. Finally, we discuss expected future challenges in UC management.
The evaluated drugs have demonstrated efficacy with an acceptable safety profile. IL-23 antagonists appear to be safest with very few (serious) adverse events, while the use of S1PR modulators or JAK inhibitors has been associated with infectious and cardiovascular/thromboembolic events, albeit in low numbers. Although advances in drug development are promising, there is an urgent need for (validated) biomarkers to guide rational treatment selection. The scarcity of head-to-head trials also complicates comparisons between available drugs. Breaking the therapeutic ceiling of efficacy in UC will require marked advances in management extending well beyond drug development.
尽管溃疡性结肠炎（UC）的医学治疗取得了进展，但仍有一部分患者对现有治疗方法没有反应。许多新型药物处于临床开发后期，或最近已获得 UC 的监管批准。
本文重点介绍了最近获得或正在等待 UC 批准的三类药物：白细胞介素（IL）-23 抗体、鞘氨醇-1-磷酸受体（S1PR）调节剂和 Janus 激酶（JAK）选择性抑制剂。我们概述了它们的作用机制，并总结了其疗效和安全性的现有证据。最后，我们讨论了 UC 管理中未来可能面临的挑战。
评估的药物具有良好的疗效和可接受的安全性。IL-23 拮抗剂的安全性似乎最高，只有极少数（严重）不良事件，而 S1PR 调节剂或 JAK 抑制剂的使用与感染和心血管/血栓栓塞事件相关，尽管数量较少。尽管药物开发取得了进展，但迫切需要（经过验证）的生物标志物来指导合理的治疗选择。缺乏头对头试验也使可用药物之间的比较变得复杂。要想在 UC 治疗中取得疗效的重大突破，需要在药物开发之外的领域取得显著进展。
