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.

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

Figures