Histological activity predicts relapse in pediatric ulcerative colitis despite mucosal healing: a multicenter study from the pediatric IBD Porto group of ESPGHAN

BACKGROUND AND AIMS: The STRIDE-II recommends mucosal healing as a treatment goal for patients with ulcerative colitis (UC), yet histological remission is increasingly recognized as a meaningful therapeutic target. This study aims to evaluate whether histological activity among patients with mucosal healing is associated with the risk of subsequent relapse. METHODS: A multicenter, retrospective cohort study comprised of 19 IBD centers from 9 countries. The study included children diagnosed with UC from January 2012 to December 2022 who had a follow-up endoscopy demonstrating mucosal healing and for whom histology scores were available. Histological remission was defined as a Nancy index (NI) ≤ 1, a Geboes score (GS) ≤ 2, or a Robarts Histopathology Index (RHI) ≤ 3. Histological healing was defined as a histological score of 0. RESULTS: We included 193 children (mean age at diagnosis 10.8 ± 4.3 years; 128 66% female). At endoscopy, 155 (80%) children were in histological remission, and 107 (55%) had histological healing. During a median follow-up of 2.4 (range 1-8.7) years, 65 (34%) children experienced a relapse. Patients with histological healing had lower relapse rates than those with residual histological activity (27% vs. 41%; P = .031). Cox regression analysis showed that the absence of histological remission was significantly associated with a higher risk of relapse during follow-up (hazard ratio HR 0.499, 95% confidence interval CI 0.289-0.863, P = .013), with an even stronger association in those without histological healing (HR 0.469, 95% CI 0.284-0.773, P = .003). CONCLUSION: Histological activity is a risk factor for relapse of UC in children with mucosal healing.