Targeting Interleukin-7 Signalling in Ulcerative Colitis: Rationale and Emerging Clinical Evidence

Ulcerative colitis (UC) remains difficult to control in a substantial proportion of patients despite an expanding range of advanced therapies. Interleukin-7 (IL-7) is a homeostatic cytokine that supports lymphocyte survival, persistence and intestinal trafficking through signalling via IL-7 receptor-α (IL-7Rα; CD127), providing a rationale for selective pathway inhibition in chronic intestinal inflammation. This narrative review examines the biology of IL-7/IL-7R signalling in inflammatory bowel disease (IBD) and summarises the preclinical, translational and clinical development of lusvertikimab, a humanised monoclonal antibody targeting IL-7Rα. MEDLINE was searched from inception to 31 July 2026, supplemented by reference-list screening, trial registries, conference proceedings and regulatory sources. Experimental studies show that IL-7 supports the persistence of colitogenic effector-memory T cells and contributes to innate immune activation. Human translational data demonstrate enrichment of IL-7R pathway activity in treatment-refractory IBD, association with anti-TNF non-response, and IL-7-mediated upregulation of the gut-homing integrin α4β7. Preclinical IL-7R blockade attenuated experimental colitis, reduced intestinal T-cell trafficking and altered inflammatory responses in UC tissue. In a first-in-human study, lusvertikimab produced sustained receptor occupancy and suppression of IL-7-associated gene expression without broad lymphocyte depletion. In the phase II CoTikiS trial, lusvertikimab improved Modified Mayo Score versus placebo, with significant pooled endoscopic improvement but no significant pooled differences in clinical or endoscopic remission. Early safety findings were reassuring. Selective IL-7Rα blockade therefore represents a biologically distinct therapeutic strategy in UC, although larger controlled studies, biomarker validation and clarification of dose selection and long-term safety are required to define its clinical role and whether combination strategies warrant future evaluation in selected patients.