{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T08:44:05Z","timestamp":1792053845592,"version":"4.4.0"},"reference-count":22,"publisher":"Maad Rayan Publishing Company","issue":"2","content-domain":{"domain":["mejdd.org"],"crossmark-restriction":false},"short-container-title":["Middle East J Dig Dis"],"published-print":{"date-parts":[[2026,4,30]]},"abstract":"<jats:p>Crohn\u2019s disease (CD) is a chronic inflammatory bowel disorder with colonic involvement in a substantial proportion of patients, often associated with increased symptom burden and therapeutic complexity. Upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, has emerged as an effective oral therapy for moderate-to-severe CD, including patients with colonic-predominant disease. This narrative review synthesizes evidence from phase 2 and 3 randomized controlled trials, post-hoc subgroup analyses, long-term extension studies, and real-world observational cohorts evaluating the efficacy and safety of upadacitinib in CD with colonic involvement. Across pivotal trials, induction therapy demonstrated superior rates of clinical remission (approximately 39-50% versus 21-29% with placebo), significant endoscopic response, and rapid symptom improvement. Maintenance therapy sustained both clinical and endoscopic outcomes through one year and beyond. Real-world studies corroborate effectiveness in highly treatment-experienced populations, although heterogeneity in study design limits causal inference. The safety profile is consistent with known JAK inhibitor class effects, with infections\u2014particularly herpes zoster\u2014requiring appropriate risk mitigation. Pharmacogenetic predictors of response to upadacitinib remain undefined, representing an important area for future research. Overall, upadacitinib constitutes a valuable therapeutic option for patients with refractory colonic CD, while comparative effectiveness and precision-medicine strategies warrant further investigation.<\/jats:p>","DOI":"10.34172\/mejdd.3467","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:46:42Z","timestamp":1792050402000},"page":"75-81","update-policy":"https:\/\/doi.org\/10.34172\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Upadacitinib in Colonic Crohn\u2019s Disease: A Narrative Review of Mechanistic Rationale, Clinical Trial Evidence, and Real-World Outcomes"],"prefix":"10.34172","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4247-3533","authenticated-orcid":true,"given":"Yousef","family":"VatanParast","sequence":"first","affiliation":[{"name":"Shafa Hospital, Jundishapur University of Medical Sciences, Ahvaz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"20123","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(16)31711-1"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0156-2"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0273-0"},{"key":"R4","unstructured":"AbbVie Inc. RINVOQ (Upadacitinib) Prescribing Information. North Chicago, IL: AbbVie Inc; 2023."},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2013.06.007"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1186\/s41927-018-0031-x"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1186\/s41927-018-0031-x"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Sandborn WJ, Feagan BG, Loftus EV Jr, Peyrin-Biroulet L, Van Assche G, D\u2019Haens G, et al. Efficacy and safety of upadacitinib in a randomized trial of patients with Crohn\u2019s disease. Gastroenterology 2020;158(8):2123-38.e8. doi:10.1053\/j.gastro.2020.01.047.","DOI":"10.1053\/j.gastro.2020.01.047"},{"key":"R9","doi-asserted-by":"crossref","unstructured":"D\u2019Haens G, Pan\u00e9s J, Louis E, Lacerda A, Zhou Q, Liu J, et al. Upadacitinib was efficacious and well-tolerated over 30 months in patients with Crohn\u2019s disease in the CELEST extension study. Clin Gastroenterol Hepatol 2022;20(10):2337-46.e3. doi:10.1016\/j.cgh.2021.12.030.","DOI":"10.1016\/j.cgh.2021.12.030"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212728"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2024.02.027"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2024.08.032"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2024.02.026"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaf138"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1111\/apt.70073"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1136\/flgastro-2024-102668"},{"key":"R17","doi-asserted-by":"crossref","unstructured":"Devi J, Xu A, Stone M, Patel A, Khan A, Reddy N, et al. Real-world effectiveness and safety of upadacitinib in Crohn\u2019s disease: a multicenter study. Clin Gastroenterol Hepatol 2025;23(12):2281-91.e4. doi:10.1016\/j.cgh.2025.01.012.","DOI":"10.1016\/j.cgh.2025.01.012"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13010190"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9121748"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26041760"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04365-8"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13688"}],"container-title":["Middle East Journal of Digestive Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/mejdd.org\/index.php\/mejdd\/article\/view\/3467\/2438","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/mejdd.org\/index.php\/mejdd\/article\/view\/3467\/2438","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:46:46Z","timestamp":1792050406000},"score":1,"resource":{"primary":{"URL":"http:\/\/mejdd.org\/index.php\/mejdd\/article\/view\/3467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":22,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,4,30]]}},"URL":"https:\/\/doi.org\/10.34172\/mejdd.3467","relation":{},"ISSN":["2008-5249"],"issn-type":[{"value":"2008-5249","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4,30]]},"assertion":[{"value":"Iranian Association of Gastroerterology and Hepatology","name":"journal_owner","label":"Journal Owner"},{"value":"Iranian Association of Gastroerterology and Hepatology","name":"journal_publisher","label":"Journal Publisher"},{"value":"2026-01-12","order":1,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}