# Poster Session II - A228 NEO-TERMINAL ILEUM HISTOLOGY PREDICTS LONG-TERM CLINICAL OUTCOMES IN POSTOPERATIVE CROHN’S DISEASE PATIENTS IN ENDOSCOPIC REMISSION

## TL;DR

This study shows that the microscopic appearance of the neo-terminal ileum in Crohn's disease patients after surgery can predict future disease flare-ups better than endoscopic exams.

## Contribution

The study introduces neo-terminal ileum histology as a novel predictor of long-term outcomes in postoperative Crohn's disease patients.

## Key findings

- Higher Robarts Histopathology Index (RHI) was linked to increased clinical recurrence.
- Biopsy area chronically inflamed predicted therapy escalation.
- Neutrophils in epithelium increased hospitalization risk.

## Abstract

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.

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.

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.

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).

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.

CIHRLunenfeld-Tanenbaum Research Institute, NIH NIDDK R01