The ileal pouch in IBD Unraveling the complexities

Approximately 10% of ulcerative colitis patients undergo a proctocolectomy within ten years of their diagnosis. An ileal pouch-anal anastomosis is the gold standard for restoring bowel continuity. While pouch patients generally experience a good quality of life, both short- and long-term complications are common.
The first part of this dissertation focuses on various outcomes and complications of the pouch, including chronic pouchitis, pre-pouch ileitis, Crohn’s-like disease of the pouch (CDP), and solitary pouch ulcers. Establishing the correct diagnosis is challenging due to the lack of clear definitions and overlapping clinical and endoscopic parameters. Patients presenting with pre-pouch ileitis or structural issues such as strictures, fistulas, or a chronic sinus are often diagnosed with CDP, even in the absence of preoperative evidence of Crohn’s disease. Our study found that nearly half of the patients diagnosed with CDP had a fistula or sinus closely associated with the anastomosis, which is indicative of (late) anastomotic leakage. As a result, these patients were incorrectly treated with medication instead of surgery. A MRI one year after surgery or at the initiation of step-up therapy is recommended to rule out postoperative complications.
The second part of the dissertation examines the effect of tofacitinib in patients with ulcerative colitis as well as those with chronic pouchitis. In our pilot study on chronic pouchitis patients, 31% achieved clinical remission, and 54% showed a clinical response after eight weeks of treatment with tofacitinib. However, endoscopic and histological scores did not significantly improve. In patients with ulcerative colitis who still had their colon in situ, tofacitinib was also investigated, with 38% showing histo-endoscopic improvement. Gene expression analysis confirmed the effect of tofacitinib on the JAK-STAT signaling pathway, and CLC (Charcot-Leyden Crystal) was identified as a potential biomarker for predicting response to tofacitinib.