Personalized Risk Stratification of Residual Histologic Activity in IBD Using Circulating Cytokines

Background: Persistent histologic inflammation may remain present in patients with inflammatory bowel disease (IBD) despite endoscopic remission. This study evaluated a clinically interpretable cytokine-based framework for risk stratification of residual histologic activity. Methods: In this prospective cohort study, 59 patients with IBD undergoing colonoscopy were included. Primary analyses were restricted to patients with ulcerative colitis (UC) in endoscopic remission (n = 31). Histologic activity was assessed using the Geboes score. Serum interleukin-10 (IL-10), interleukin-23 (IL-23), and C-reactive protein (CRP) were measured prior to endoscopy. Receiver operating characteristic (ROC) analysis and ROC-derived thresholds were used to evaluate biomarker performance and construct a cytokine-based risk stratification framework. Results: Among patients with UC in endoscopic remission, 14/31 (45.2%) demonstrated persistent histologic activity. IL-10 showed the strongest discriminatory performance for histologic activity (AUC 0.850), with a threshold < 3.9 pg/mL associated with sensitivity of 84.6% and specificity of 77.8%. Similar performance was observed using raw assay-reported IL-10 values (AUC 0.906). IL-23 showed limited overall discrimination (AUC 0.615). A combined IL-10/IL-23 framework stratified patients into progressively higher-risk subgroups, with histologic activity observed in 1/14 patients (7.1%) in the low-risk subgroup, 1/2 patients (50.0%) in the Intermediate A subgroup, 9/12 patients (75.0%) in the Intermediate B subgroup, and 3/3 patients (100%) in the high-risk subgroup (p < 0.001), although estimates for smaller subgroups should be interpreted cautiously. Reduced IL-10 levels were independently associated with histologic activity, whereas IL-23 primarily refined subgroup classification without substantially improving discrimination. Conclusions: An exploratory cytokine-based framework incorporating IL-10 and IL-23 may support risk stratification of residual histologic activity in UC during endoscopic remission. Larger multicenter studies are required to validate these findings and define their clinical utility.