P082 PREOPERATIVE ANTI-TNFS ARE ASSOCIATED WITH A SHORTER INTERVAL TO DE NOVO CROHN’S DISEASE AFTER ILEAL POUCH-ANAL ANASTOMOSIS FOR ULCERATIVE COLITIS

Abstract

Anti-tumor necrosis factor (anti-TNF) agents are widely used in the treatment of moderate to severe ulcerative colitis (UC) since commercial approval in 1998. Many patients however ultimately require surgery with ileal pouch-anal anastomosis (IPAA). Conversion of UC to Crohn’s disease (CD) following IPAA is a devastating complication termed de novo Crohn’s disease (DNCD). Despite increasing adoption, few prior studies have evaluated the effect of preoperative anti-TNFs on DNCD development. As we have noticed an increasing incidence of DNCD, we hypothesized that preoperative utilization of anti-TNFs may be associated with the development of DNCD after IPAA. A prospective inflammatory bowel disease (IBD) registry was queried for consecutive UC patients undergoing IPAA during the 25-year period ending 2018. Patients with preoperative CD or IBD unclassified were excluded. De novo CD after IPAA was diagnosed when 5 or more ulcers involving the small-bowel proximal to the ileal pouch or a pouch fistula or other perianal complication developed >3 months after ileostomy closure. Preoperative anti-TNF therapy and development of DNCD was compared between 3 chronologic periods throughout the study: period 1: 1993-1998 (pre-approval of anti-TNFs for UC), period 2: 1999-2008, and period 3: 2009-2018. Cox proportional-hazards model was used to identify predictors of DNCD development. The study cohort consisted of 400 patients (38.5 ± 16 years; males n=205, 51%; Table 1). Sixty-two patients (16%), 31 (50%) of whom were male, developed DNCD after IPAA during a mean follow-up period of 98 ± 67 months. The incidence of DNCD was similar between periods (n=8 [15%] during period 1; n=37 [20%] during period 2; n=17 [11%] during period 3; p=0.07). Usage of anti-TNFs increased during each successive period (n=0 [0%] during period 1, n=40 [22%] during period 2, n=125 [79%] during period 3; p<0.001) while time to DNCD decreased (mean time 87 ± 104 months during period 1; 53 ± 52 months during period 2; 18 ± 22 months during period 3; p=0.01). Incidence of DNCD was similar in anti-TNF treated (45%) compared to anti-TNF naïve patients (41%; p=0.58) but the time to de novo CD was significantly shorter in anti-TNF treated (27 ± 39 months) versus anti-TNF naïve patients (64 ± 66 months; p=0.008). Cox proportional hazards model identified preoperative anti-TNF therapy as an independent risk factor for development of DNCD after IPAA (HR 2.82; 95% CI 1.65 – 4.83; p<0.001). A Kaplan-Meier survival curve illustrates the significant difference in CD-free survival between anti-TNF treated compared to anti-TNF naïve patients (Figure 1; Log rank p=0.007). Preoperative utilization of anti-TNFs may play a significant role in the earlier development of DCND following IPAA. Figure 2. De novo Crohn’s Disease-Free Survival Based on Treatment with Anti-TNF