THE CHANGING DISEASE PARADIGM IN INFLAMMATORY BOWEL DISEASE: FROM SYMPTOM CONTROL TO DISEASE MODIFICATION

Shashikant Adlekha; Tandra Chadha; Yash Vinay Gaiakward; DeAsia Lewis; Myonna Petty; Laura Tedesco

Shashikant Adlekha ¹, Tandra Chadha ², Yash Vinay Gaiakward ³, DeAsia Lewis ⁴, Myonna Petty ⁵, Laura Tedesco ⁶

¹ Department of Pathology, Trinity Medical Sciences University, Saint Vincent and the Grenadines. (corresponding author)

² Department of Microbiology and Immunology, Trinity Medical Sciences University, Saint Vincent and the Grenadines.

³ MD student, Trinity Medical Sciences University, Saint Vincent and the Grenadines.

⁴ MD student, Trinity Medical Sciences University, Saint Vincent and the Grenadines.

⁵ MD student, Trinity Medical Sciences University, Saint Vincent and the Grenadines.

⁶ MD student, Trinity Medical Sciences University, Saint Vincent and the Grenadines.

Published 2026-08-20 · pp. 282-288

Abstract

Inflammatory bowel disease, comprising Crohn's disease and ulcerative colitis, is a chronic immune-mediated disorder of rising global prevalence and heterogeneous course. Management has historically been directed at relieving patient-reported symptoms, an approach that has not prevented the accumulation of irreversible bowel damage. Over the past decade the field has moved towards disease modification, in which therapy is guided by objective measures of inflammation and the goal is preservation of bowel function rather than short-term symptom suppression.

This narrative review examines that transition. Successive iterations of the Selecting Therapeutic Targets in Inflammatory Bowel Disease initiative have formalised a hierarchy of treat-to-target endpoints, from clinical response through biochemical and endoscopic remission towards histologic and transmural healing. The CALM trial established that biomarker-guided tight control improves endoscopic outcomes relative to symptom-driven escalation, and the PROFILE trial demonstrated that early combined immunosuppression at diagnosis substantially improves one-year outcomes in Crohn's disease, although the prognostic biomarker it tested did not show clinical utility. Transmural healing, assessed by magnetic resonance enterography or intestinal ultrasonography, has emerged as a candidate endpoint in Crohn's disease, and histologic remission and the aspirational concept of disease clearance are being explored in ulcerative colitis.

Substantial gaps remain. Standardised definitions of disease modification and of transmural healing are lacking, predictive biomarkers that reliably forecast therapeutic response are limited, and it has not been demonstrated that deeper endpoints confer prognostic value beyond endoscopic remission. Much of the supporting evidence for the deepest targets remains observational. The review synthesises current evidence on therapeutic endpoints, treat-to-target frameworks and precision medicine, and identifies what would be required to translate symptom control into validated disease modification.

Keywords: Inflammatory bowel disease; Crohn's disease; ulcerative colitis; disease modification; mucosal healing; transmural healing; treat-to-target; precision medicine.