Intestinal Barrier Healing Is Superior to Endoscopic and Histologic Remission for Predicting Major Adverse Outcomes in Inflammatory Bowel Disease: The Prospective ERIca Trial

BACKGROUND & AIMS: Endoscopic and histologic remission have emerged as key therapeutic goals in the management of inflammatory bowel diseases (IBD) that are associated with favorable long-term disease outcomes. Here, we prospectively compared the predictive value of barrier healing with endo-scopic and histologic remission for predicting long-term disease behavior in a large cohort of patients with IBD in clinical remission. METHODS: At baseline, patients with IBD in clinical remission underwent ileocolonoscopy with assessment of intes-tinal barrier function by confocal endomicroscopy. Endoscopic and histologic disease activity, as well as barrier healing, was prospectively assessed along established scores. During subse-quent follow-up, patients were closely monitored for clinical disease activity and the occurrence of major adverse outcomes (MAOs): disease flares, IBD-related hospitalization or surgery, and initiation or dose escalation of systemic steroids, immuno-suppressants, small molecules, or biological therapy. RESULTS: The final analysis included 181 patients, 100 with Crohn's dis-ease [CD] and 81 with ulcerative colitis (UC). During a mean follow-up of 35 (CD) and 25 (UC) months, 73% of patients with CD and 69% of patients with UC experienced at least 1 MAO. The probability of MAO-free survival was significantly higher in patients with IBD with endoscopic remission compared with endoscopically active disease. In addition, histologic remission predicted MAO-free survival in patients with UC but not CD. Barrier healing on endomicroscopy was superior to endoscopic and histologic remission for predicting MAO-free survival in both UC and CD. CONCLUSIONS: Barrier healing is associated with decreased risk of disease progression in patients with clin-ically remittent IBD, with superior predictive performance compared with endoscopic and histologic remission. Analysis of barrier function might be considered as a future treatment target in clinical trials. ClinicalTrials.gov number, NCT05157750.