P269 Phenotypic predictors of endoscopic recurrence after ileal resection for Crohn's disease: an NIDDK IBD Genetics Consortium prospective study

Abstract

Introduction: Disease recurrence in patients after ileal resection of Crohn's Disease (CD) is predictable and represents an excellent model to study the mechanisms of intestinal inflammation in an at-risk population. Our aim is to investigate genomic and microbial factors associated with post-operative endoscopic recurrence. Here we present preliminary phenotypic analysis of recruited subjects to a prospective NIDDK Inflammatory Bowel Disease Genetics Consortium longitudinal study. Method(s): Patients with CD scheduled to undergo ileocolic resection with primary anastomosis were recruited at 6 North American research centers using a standardized protocol. Clinical data and bio specimen collection for microbiome and histological assessment was performed pre-operatively and at follow up visits. A Rutgeert's score of at least i2 was defined as endoscopic recurrence. Bivariate analysis (c2 test) was performed using Graphpad. Result(s): 294 patients were enrolled up to August 2016 and 122 had at least 1 post-operative endoscopy. The overall recurrence rate in the neoterminal ileum up to 18 months was 33.6% (n=41/122). Early endoscopic recurrence was present in 23.7% (n=29/122) at a median 6 months. CD recurrence was not significantly associated with Montreal classification, age, gender, smoking, or previous hospitalizations. Patients with a prior history of ileal resection had a higher risk of post-operative recurrence (P=0.004, RR 2.6 95% CI [1.5-3.8], n=9/41 vs n=3/81). Peri operative steroids (P=0.002, RR 3.4 95% CI [1.46-8.9]), combined immune suppressants and anti-TNF agents (P=0.028, RR infinity) and anti-TNF monotherapy use (P=0.056, RR 1.03 95% CI [1.002-4.04]) were associated with a reduction in the likelihood of endoscopic recurrence. Use of anti-TNF therapy post-operatively was also associated with reduced recurrence rate (P=0.03, RR 2.81 95% CI [1.18-7.3], 15.7%, n=6/38 vs 41.6%, n=35/84). Patients recruited in the USA were more likely to receive anti-TNF therapy prior to first post-operative endoscopy (P=0.02, RR 2 95% CI l1.4-3.6]). Early recurrence rates were higher in Canadian centers although this was not statistically significant (P=0.45 [20% vs 40%]). Conclusion(s): Preliminary phenotypic results showed that previous surgery predicted endoscopic post-operative recurrence, potentially indicating a more aggressive phenotype. Steroid exposure perioperatively and use of anti-TNF biologic therapy peri- and post-operatively before colonoscopy were associated with lower risk of endoscopic recurrence, validating studies which show benefit of anti-TNF in prevention of post-operative recurrence. Future studies in this population will investigate microbial and transcriptomic profiles related to disease recurrence and ongoing recruitment will further expand our cohort.