Targeted Therapies in Inflammatory Bowel Disease: Mechanisms, Comparative Evidence, and Clinical Translation
TL;DR
The current evidence supports mechanism-informed rather than biomarker-defined treatment selection, and the mechanistic rationale, comparative clinical evidence, and translational implications of approved and emerging targeted therapies for adult IBD are examined.
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn’s 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–tumour 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.