Choi Yunseok, Lee Suhyun, Kim Hyeon Ji, Park Taemin, Kwack Won Gun, Yang Seungwon, Chung Eun Kyoung
Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
Department of Pharmacy, College of Pharmacy, Woosuk University, Wanju 55338, Republic of Korea.
Pharmaceuticals (Basel). 2025 May 17;18(5):740. doi: 10.3390/ph18050740.
: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation and incomplete response to conventional therapies. Although biologics have advanced UC management, many patients with moderate-to-severe disease experience treatment failure, relapse, or adverse effects. This review evaluates the pharmacology, efficacy, and safety of oral Janus kinase (JAK) inhibitors-tofacitinib, upadacitinib, and filgotinib-to guide their clinical use in UC. : A comprehensive literature review was conducted using the PubMed, Embase, Cochrane, and Web of Science databases to identify relevant studies on JAK inhibitors in UC. The review included Phase 3 randomized controlled trials (RCTs), real-world observational studies, and recent network meta-analyses. We assessed pharmacologic profiles, clinical efficacy, and safety data for tofacitinib, upadacitinib, and filgotinib. Additionally, we reviewed emerging pipeline agents and future directions in oral immunomodulatory therapy for UC. : All three agents demonstrated efficacy in the induction and maintenance of remission. Upadacitinib showed superior performance, including rapid symptom control, high clinical remission rates, and favorable long-term outcomes in both biologic-naïve and -experienced patients. Tofacitinib offered strong efficacy, particularly in early response, but was associated with higher risks of herpes zoster and thromboembolic events. Filgotinib provided moderate efficacy with a favorable safety profile, making it suitable for risk-averse populations. Meta-analyses consistently ranked upadacitinib highest in clinical efficacy and onset of action. : JAK inhibitors offer effective and convenient oral treatment options for moderate-to-severe UC. Upadacitinib emerges as a high-efficacy agent; tofacitinib and filgotinib remain valuable based on patient-specific risk profiles. Future studies are needed to clarify optimal sequencing, long-term safety, and the role of emerging agents or combination therapies.
溃疡性结肠炎（UC）是一种慢性炎症性肠病，其特征为炎症反复发作且对传统疗法反应不完全。尽管生物制剂改善了UC的治疗，但许多中重度疾病患者仍经历治疗失败、复发或出现不良反应。本综述评估口服Janus激酶（JAK）抑制剂托法替布、乌帕替尼和非戈替尼的药理学、疗效和安全性，以指导它们在UC中的临床应用。：使用PubMed、Embase、Cochrane和Web of Science数据库进行了全面的文献综述，以识别关于JAK抑制剂在UC中的相关研究。该综述包括3期随机对照试验（RCT）、真实世界观察性研究和近期的网络荟萃分析。我们评估了托法替布、乌帕替尼和非戈替尼的药理学特征、临床疗效和安全性数据。此外，我们还综述了UC口服免疫调节治疗中新兴的在研药物和未来方向。：所有三种药物在诱导和维持缓解方面均显示出疗效。乌帕替尼表现更优，包括症状快速控制、临床缓解率高以及在未使用过生物制剂和使用过生物制剂的患者中均有良好的长期疗效。托法替布疗效显著，尤其是早期反应，但与带状疱疹和血栓栓塞事件的较高风险相关。非戈替尼疗效中等且安全性良好，适用于风险规避人群。荟萃分析一致将乌帕替尼的临床疗效和起效速度排在首位。：JAK抑制剂为中重度UC提供了有效且便捷的口服治疗选择。乌帕替尼是一种高效药物；托法替布和非戈替尼根据患者特定的风险特征仍具有价值。未来需要开展研究以阐明最佳用药顺序、长期安全性以及新兴药物或联合疗法的作用。
