{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:16:16Z","timestamp":1788243376919,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Inflammatory bowel disease (IBD), encompassing Crohn\u2019s disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated condition with substantial global burden and rising incidence, requiring an expanding range of advanced therapies. This focused narrative review examines the mechanistic rationale, comparative clinical evidence, and translational implications of approved and emerging targeted therapies for adult IBD. A structured literature search was conducted in PubMed, Scopus, and Web of Science for publications from January 2021 to March 2026. Thirty-eight articles were selected as the core evidence set with landmark trials and clinical guidelines added when needed for historical or practice context. Evidence was synthesised narratively, with an explicit distinction between direct head-to-head comparisons, placebo-controlled trials, indirect network comparisons, and observational data. In UC, VARSITY showed higher week-52 clinical remission and endoscopic improvement with vedolizumab than adalimumab; in CD after anti\u2013tumour necrosis factor (anti-TNF) failure, SEQUENCE showed risankizumab noninferior to ustekinumab for week-24 clinical remission and superior for week-48 endoscopic remission. Agents targeting tumour necrosis factor-like cytokine 1A (TL1A) have shown encouraging activity in phase 2\/2b trials, but long-term effectiveness and safety remain uncertain. The current evidence supports mechanism-informed rather than biomarker-defined treatment selection. Confidence in comparative conclusions is greatest when supported by direct randomised evidence, whereas observational and indirect comparisons require caution because of confounding, heterogeneity, and differences in populations and outcome definitions. Clinical translation therefore requires the integration of the disease phenotype, prior treatment exposure, safety risks, and patient preference, with objective reassessment after therapy initiation.<\/jats:p>","DOI":"10.3390\/jcm15176753","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:45:13Z","timestamp":1788241513000},"page":"6753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Therapies in Inflammatory Bowel Disease: Mechanisms, Comparative Evidence, and Clinical Translation"],"prefix":"10.3390","volume":"15","author":[{"given":"Christopher","family":"Pavel","sequence":"first","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Popa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalina","family":"Ilie","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5730-9381","authenticated-orcid":false,"given":"Oana-Mihaela","family":"Plotogea","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raluca-Ioana","family":"Dascalu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodor","family":"Cabel","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2984-4727","authenticated-orcid":false,"given":"Deniz","family":"Gunsahin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4133-5726","authenticated-orcid":false,"given":"Iulia","family":"Tincu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Pediatrics, \u201cDr. Victor Gomoiu\u201d Children\u2019s Clinical Hospital, 022102 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0056-0740","authenticated-orcid":false,"given":"Bogdan","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Surgery, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza Elena","family":"Pavel","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Pathology, Emergency University Hospital, 050098 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Oaie","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1007\/s10787-024-01508-w","article-title":"Efficacy and safety of infliximab and adalimumab in 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