TL1A as a therapeutic renaissance in inflammatory bowel disease: a systematic review from molecular mechanisms to clinical translation

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dc.contributor.authorLiang, Raymond Fueng Hin
dc.contributor.authorPugliano, Cecilia Lina
dc.contributor.authorHughes, Robert
dc.contributor.authorMajumder, Snehali
dc.contributor.authorLo Bello, Antonio
dc.contributor.authorIacucci, Marietta
dc.contributor.authorGhosh, Subrata
dc.date.accessioned2026-09-08T10:57:01Z
dc.date.available2026-09-08T10:57:01Z
dc.date.issued2026-05-05
dc.description.abstractBackground and Aims: Despite major therapeutic advances, many patients with inflammatory bowel disease (IBD) continue to experience inadequate treatment response, progressive disease, and irreversible complications requiring surgery. Current management is constrained by a biological efficacy ceiling and lack of agents directly targeting key drivers of fibrosis and barrier dysfunction. This systematic review synthesizes current knowledge on tumor necrosis factor-like cytokine 1A (TL1A) and death-domain receptor 3 (DR3) signaling pathways, critically evaluates the therapeutic potential of TL1A-targeted interventions, and explores future directions for precision medicine applications in IBD care. Methods: A comprehensive systematic search of PubMed, EMBASE, Cochrane library, Web of Science, and ClinicalTrials.gov was conducted according to PRISMA guidelines. Three independent reviewers screened preclinical and clinical studies using Rayyan software. Study selection, data extraction, and quality assessment were performed in duplicate. Eligible studies underwent narrative thematic synthesis. Results: Of 250 studies identified, 63 met inclusion criteria. Preclinical data consistently demonstrate TL1A-DR3 signaling drives inflammation, fibrosis, and barrier dysfunction. Phase 2 clinical trials showed anti-TL1A monoclonal antibodies (Tulisokibart, Afimkibart, Duvakitug) achieved clinical remission/response rates between 26% and 66% in patients with moderate-to-severe IBD at 12-14 weeks, with favorable safety profiles. Emerging themes include extended dosing intervals, therapeutic benefit in treatment-refractory populations, potential anti-fibrotic effects, and opportunities for biomarker-guided patient stratification. Conclusion: TL1A inhibitors represent a promising novel therapeutic class with dual anti-inflammatory and anti-fibrotic properties, addressing critical unmet clinical needs in IBD. These agents hold the potential to become cornerstone therapies in the evolving landscape of precision medicine for IBD care.en
dc.description.versionPublished Version
dc.format.extent13
dc.format.mimetypeapplication/pdfen
dc.identifier.articleidjjag039
dc.identifier.authororcidLiang, Raymond Fueng Hin
dc.identifier.authororcidPugliano, Cecilia Lina
dc.identifier.authororcidHughes, Robert
dc.identifier.authororcidMajumder, Snehali
dc.identifier.authororcidLo Bello, Antonio
dc.identifier.authororcidIacucci, Marietta
dc.identifier.authororcidGhosh, Subrata
dc.identifier.citationLiang, R F H, Pugliano, C L, Hughes, R, Majumder, S, Lo Bello, A, Iacucci, M & Ghosh, S 2026, 'TL1A as a therapeutic renaissance in inflammatory bowel disease: a systematic review from molecular mechanisms to clinical translation', Journal of Crohn's and Colitis, vol. 20, no. 5, jjag039, pp. 1-13. https://doi.org/10.1093/ecco-jcc/jjag039
dc.identifier.doi10.1093/ecco-jcc/jjag039
dc.identifier.endpage13
dc.identifier.issn1873-9946
dc.identifier.issued5
dc.identifier.startpage1
dc.identifier.urihttps://hdl.handle.net/10468/19185
dc.identifier.volume20
dc.language.isoen
dc.publisherOxford University Press
dc.relation.urihttps://www.scopus.com/pages/publications/105039787105
dc.rights© 2026, the Author(s). Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
dc.rights.accessrightsopen access
dc.rights.licensenameAttribution-NonCommercial 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.statusPeer reviewed
dc.subjectAnti-fibrotic
dc.subjectAnti-TL1A
dc.subjectInflammatory bowel disease
dc.subjectPrecision medicine
dc.subject[APCMicrobiome]
dc.subject[Medicine]
dc.titleTL1A as a therapeutic renaissance in inflammatory bowel disease: a systematic review from molecular mechanisms to clinical translationen
dc.typeReview
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