Poster Session II - A227 NEO-TERMINAL ILEUM HISTOLOGY PREDICTS LONG-TERM CLINICAL OUTCOMES IN POSTOPERATIVE CROHN’S DISEASE PATIENTS IN ENDOSCOPIC REMISSION

Abstract Background Crohn’s disease (CD) is characterized by chronic inflammation of the digestive tract, where surgery may often be required. Postoperative (post-op) recurrence remains common and difficult to predict. Although certain microbial taxa have been identified, other potential predictors, including the histological appearance of the neo-terminal ileal (neo-TI) mucosa, are not well defined. Aims This study aims to evaluate the association between histological features from the neo-TI and long-term clinical outcomes in post-op CD patients who are in endoscopic remission. Methods In this prospective study, CD patients who underwent ileocolic resection at Mount Sinai Hospital, Toronto, with neo-TI biopsies at ∼6 months post-op were recruited. We included patients in endoscopic remission (mRutgeerts≤i2a) at the 1st post-op colonoscopy. The primary outcome was time-to-clinical recurrence (CR), defined as the presence of CD symptoms and objective evidence of inflammation by imaging, endoscopy, or lab tests (CRP>5 mg/L or Fecal Calprotectin>250 ug/g), within 6 months of onset. Secondary outcomes included time-to-therapy initiation/escalation, CD-related hospitalization, and global recurrence (any of the events above). A comprehensive neo-TI histology assessment items were determined by expert IBD pathologists (J.C., R.R.). Neo-TI histology, including Robarts Histopathology Index (RHI) and various features that are not part of the traditional grading schemes, was evaluated (J.C.), blinded to clinical outcomes. A multivariable Cox proportional hazards model accounting for confounders (e.g., prior resection, post-op biologic use) was utilized. Results 79 CD patients in endoscopic remission at the 1st post-op colonoscopy was included. Increased RHI was significantly associated with increased CR (adjusted HR = 1.49 per SD, 95%CI: 1.02–2.18, p = 0.041). Biopsy area chronically inflamed was independently associated with increased risk of therapy escalation (aHR=1.74 per SD, 95%CI: 1.21–2.50, p = 0.003). In contrast, increased neutrophils in epithelium (5-50% vs 0% of crypts) was associated with increased risk of CD-related hospitalization (aHR=3.55, 95%CI: 1.05-11.96, p = 0.041). Interestingly, high RHI, determined using an optimized cutoff, demonstrated greater predictive performance for global recurrence (C-index=0.661) compared to the endoscopic activity (mRutgeerts Score) (C-index=0.628). Conclusions In post-op CD patients in endoscopic remission, histological features in mucosal biopsies from the neo-TI were associated with long-term clinical outcomes, with higher predictive performance compared to the endoscopic score. Further validation on the role of neo-TI histology as early markers of the post-op disease course is warranted. Funding Agencies CIHRLunenfeld-Tanenbaum Research Institute, NIH NIDDK R01