{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:11:52Z","timestamp":1788315112133,"version":"build-2803163510"},"reference-count":99,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T00:00:00Z","timestamp":1747440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Food and Drug Safety","award":["21153MFDS601-1"],"award-info":[{"award-number":["21153MFDS601-1"]}]},{"name":"Ministry of Food and Drug Safety","award":["RS-2024-00331810"],"award-info":[{"award-number":["RS-2024-00331810"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: 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\u2014tofacitinib, upadacitinib, and filgotinib\u2014to guide their clinical use in UC. Methods: 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. Results: 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-na\u00efve 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. Conclusions: 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.<\/jats:p>","DOI":"10.3390\/ph18050740","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:54:28Z","timestamp":1747724068000},"page":"740","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["State-of-the-Art Evidence for Clinical Outcomes and Therapeutic Implications of Janus Kinase Inhibitors in Moderate-to-Severe Ulcerative Colitis: A Narrative Review"],"prefix":"10.3390","volume":"18","author":[{"given":"Yunseok","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Pharmacy, College of Pharmacy, Woosuk University, Wanju 55338, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Ji","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Regulatory Innovation through Science, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taemin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Regulatory Innovation through Science, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9611-4341","authenticated-orcid":false,"given":"Won Gun","family":"Kwack","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungwon","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Regulatory Innovation through Science, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9200-2799","authenticated-orcid":false,"given":"Eun Kyoung","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Pharmacy, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea"},{"name":"Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1093\/ibd\/izaa318","article-title":"Clinical and Mechanistic Characteristics of Current JAK Inhibitors in IBD","volume":"27","author":"Pippis","year":"2021","journal-title":"Inflamm. 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