Antitumour necrosis factor therapy is associated with de novo Crohn’s disease after ileal pouch‐anal anastomosis

Abstract

Aim Tumour necrosis factor inhibitors (TNFi) have revolutionized the management of moderate to severe ulcerative colitis (UC) since their approval for UC in 2005. However, many patients ultimately require surgery with ileal pouch‐anal anastomosis (IPAA). Development of de novo Crohn's disease (CD) following IPAA is an increasingly common and devastating complication, sometimes progressing to pouch failure. The aim of this study was to evaluate the association of preoperative TNFi exposure and the development of de novo CD after IPAA. Method A prospective single‐centre inflammatory bowel disease (IBD) registry was searched for consecutive patients with UC undergoing IPAA during a 25‐year period ending July 2018. Patients with preoperative CD or IBD‐unclassified were excluded. De novo CD was diagnosed upon endoscopic evidence of five or more mucosal ulcers proximal to the ileal pouch any time after surgery and/or pouch fistula occurring more than three months after ileostomy closure. Results The study cohort consisted of 400 patients with a median follow‐up of 44.0 (IQR 11–113) months. Sixty‐two (16%) patients developed de novo CD 28.0 (IQR 6–67) months following ileostomy closure. Survival analysis of TNFi era patients revealed a significant increase in de novo CD risk in those with preoperative TNFi exposure. Multivariable proportional hazards modelling revealed two independent predictors for de novo CD development: older age was protective (HR 0.89 per 5‐year increase; P = 0.009) and preoperative TNFi exposure was hazardous (HR 2.10; P = 0.011). Conclusion This prospective study is the first to suggest an association between preoperative TNFi exposure and the development of de novo CD.

Review of long‐term complications and functional outcomes of ileoanal pouch procedures in patients with inflammatory bowel disease

“…Reported CDP incidence ranged from 7.8% to 20.9% (median 15.2%, IQR: 10%–18.75%) with a mean follow‐up time of 8.4 years 6,7,16,17,26,28,35,39,40 …”

“…Reported CDP incidence ranged from 7.8% to 20.9% (median 15.2%, IQR: 10%-18.75%) with a mean follow-up time of 8.4 years. 6,7,16,17,26,28,35,39,40 Cuffitis Four studies reported incidences of cuffitis defined as clinical symptoms characteristic of cuffitis as well as endoscopic evidence of inflammation of the remnant rectal cuff.…”

Predictors of pouch failure: A tertiary care inflammatory bowel disease centre experience

“…However, the impact of pre‐colectomy biologics on long‐term pouch outcomes is not well established. In a prospective study of 400 patients with UC who underwent TPC with IPAA, there was a significant association between pre‐colectomy exposure to tumour necrosis factor inhibitors (TNFi) and the development of ‘de novo CD’ [19]. This may, in part, be due to the theorized priming of the small bowel that occurs with exposure to TNFi pre‐colectomy and the post‐IPAA mucosal activation that occurs with faecal stasis and microbial dysbiosis and triggers CDLPI.…”

Ileal Pouch-Anal Anastomosis in the Older Adult: a Review of Postoperative Outcomes and Pouchitis Treatment

“…The literature surrounding pouchitis in the older IPAA population is mixed, with some studies reporting an increased rate of pouchitis in this population [4] whereas others have reported the same or decreased frequency [22,42]. Interestingly, older age seems to be protective against the development of Crohn's disease (or Crohn's-like disease) of the pouch, which is a long-term inflammatory condition of the ileal pouch often requiring biologic therapy [42][43][44]. Though the reason for this is unclear, this may result from younger patients being exposed to a greater variety of microbial antigens as compared to older adults, leading to greater immune reactivity [45].…”