Pre-pouch ileitis, developing in about 10% to 15% of patients who undergo ileal-pouch anal anastomosis (IPAA), is associated with a higher risk of complicated disease and pouch failure than pouchitis and should be considered a feature of Crohn’s disease (CD), Gaurav Syal, MD, explains. “Pre-pouch ileitis, or inflammation in the afferent limb of the ileal pouch, is generally regarded as a sign of CD, but there has been no strong evidence to support this,” he says. “One way to prove that pre-pouch ileitis is a feature of CD is to study whether these patients go on to develop complications like strictures and fistulae, which are well-known to occur in patients with CD.”

For a paper published in the Journal of Crohn’s and Colitis, Dr. Syal and colleagues utilized a database of patients who underwent IPAA surgery to compare the outcomes of patients who developed pre-pouch ileitis with those of patients who had pouchitis without pre-pouch ileitis. The researchers assigned 66 patients to each group. “The main outcomes of interest were development of CD-like complications like strictures and perianal fistulae and pouch failure,” says Dr. Syal.

Pre-Pouch Ileitis Associated With Aggressive Disease Course

The study team found that CD-like complications and pouch failure developed in 36.4% and 7.6% of patients in pre-pouch ileitis group, respectively, and in 10.6% and 1.5% of those in the pouchitis group, respectively. “CD-like complications-free survival and pouch failure-free survival were significantly lower in the pre-pouch ileitis group, according to Dr Syal. The pre-pouch ileitis group also had a higher risk of requiring surgical/endoscopic interventions and immunosuppressive therapy. Pre-pouch ileitis was independently associated with an increased risk of CD-like complications, need for surgical/endoscopic intervention, and immunosuppressive therapy.

“Pre-pouch ileitis is a strong, independent risk factor for development of CD-like complications like strictures and perianal fistulae, and its presence is associated with an almost four-fold increase in the risk of these complications,” says Dr. Syal (Table). “Not only does pre-pouch ileitis increase the risk of CD-like complications, it is also independently linked with a four-fold increase in the need for surgical and endoscopic interventions, and a five-fold increase in the need for immunosuppressive therapy. These findings underscore the association of pre-pouch ileitis with a more aggressive disease course compared to pouchitis alone.”

Pre-Pouch Ileitis a Feature of Crohn’s Disease

As a result of these findings, Dr. Syal and colleagues stress that physicians, particularly gastroenterologists, should regard pre-pouch ileitis as a feature of CD. “I would recommend that doctors seeing a patient with significant pre-pouch ileitis should consider treating that patient as they would treat any other patient with CD, preferably with biologic therapy,” he explains. “If the patient, physician, or both is/are not ready to start treatment for CD, the patient should be closely monitored with serial pouchoscopies at the very least.”

Patients with pouchitis and pre-pouch ileitis are at a higher risk of developing CD-like complications, requiring surgical or endoscopic interventional procedures and being treated with immunosuppressive therapy compared with patients with pouchitis alone,” he adds. “Therefore, pre-pouch ileitis should not be regarded as mere extension of pouch inflammation into the afferent limb. Given the risk of development of complications associated with pre-pouch ileitis, it should be considered a feature of de novo CD and treated proactively.”

Though this study was reportedly the largest reported observational study on pre-pouch ileitis, Dr. Syal points out that the patient sample size was rather small. “Pre-pouch ileitis in patients with IPAA is an uncommon occurrence and finding a large group of such patients to study is challenging, especially at a single center,” he says. “In future research, I would ideally like to see a prospective observational study with a larger sample in order to evaluate the outcomes of patients with pre-pouch ileitis. However, such studies might be difficult to perform and will take many years to complete. Hence, collaborative, multi-center studies, performed using an approach similar to that which we used in our study, can be a more practical way to validate our findings in a larger population.”

Dr. Syal also notes that “precision medicine research can potentially help us identify biomarkers that can predict which specific patients with pre-pouch ileitis will develop CD-like complications. In this way, we can direct our best therapeutic efforts to this subgroup of patients.”