Millie Long, MD, on Disorders of the Pouch Following IPAA

Despite improvements in medical therapy for ulcerative colitis (UC), colectomy with ileal pouch-anal anastomosis (IPAA) remains a common surgery, and a significant percentage of those patients may develop pouchitis and pouch-related conditions, Millie Long, MD, said at the Advances in Inflammatory Bowel Diseases regional meeting.

Dr Long is a professor of medicine in the division of gastroenterology and hepatology at the University of North Carolina School of Medicine in Chapel Hill, North Carolina.

“Approximately 13-15% of patients with ulcerative colitis will require a colectomy within 10 years of diagnosis,” she explained. “In cases of colectomy for refractory colitis due to UC or UC-related dysplasia, restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the preferred surgical intervention.”

Acute pouchitis is typically treated with ciprofloxacin, metronidazole, or a combination for 2 weeks; in the case of relapse additional courses of ciprofloxacin with our without metronidazole are repeated for 2 to 4 weeks/

Chronic pouchitis affects 17-19% of patients, Dr Long noted. Chronic antibiotic-dependent pouchitis (CADP) is defined by more than 4 pouchitis episodes per year; symptoms are controlled on antibiotics but worsen when antibiotics are discontinued.

Chronic antibiotic-refractory pouchitis (CARP) is defined as lack of response to normal antibiotic regimens. “Patients with this type of pouchitis may require immunosuppression, such as biologics, Dr Long explained. Recent studies have shown that biologic therapies for CARP, including ustekinumab, vedolizumab, and antitumor necrosis factor (TNF) agents can produce long-term clinical response rates of more than 70% and long-term clinical remission rates ranging from 37% to 60%.

A condition called Crohn’s-like disease of the pouch is characterized by the development of fistulae, prepouch ileitis, granulomas, and/or strictures. Dr Long said, “I’m careful to call this Crohn’s-like disease of the pouch, because we don’t know that this truly Crohn’s, and it can be devastating to a patient who has had ulcerative colitis to be told that they have Crohn’s. In reality, we just know that it has some of the clinical characteristics of Crohn’s and we’re treating it like Crohn’s because those are the agents we have.”

Various types of biologic therapy have demonstrated some efficacy in treating this condition, Dr Long explained, including anti-TNF therapy; vedolizumab, which in a multicenter study from 5 academic IBD centers showed rates of up to 71% clinical response; and ustekinumab, which demonstrated 83% clinical response in a study from 4 academic IBD centers.

Most patients who undergo IPAA have already been treated with biologics, she pointed out. A retrospective study of “recycling” precolectomy biologics was conducted at Mt. Sinai in New York among 83 adults with medically-refractory UC who underwent total proctocolectomy with IPAA and then developed a chronic inflammatory condition of the pouch. The patients who had been treated with an anti-TNF prior to total proctocolectomy with IPAA (n=44, 53%) and had experienced secondary loss of response were significantly less likely to achieve remission of chronic pouchitis if treated with the same anti-TNF after IPAA.

“Cuffitis is a residual effect of ulcerative colitis,” Dr Long said. “It’s inflammation of the remaining anorectal tissue above the dentate line; typically, a 1-2 centimeter area of rectal cuff/anal transition zone mucosa is present.” Risk factors for cuffitis include a rectal cuff length of more than 2 cm and a stapled anastomosis, she noted. “Traditional prevalence estimates are about 10-30% of patients, and it has significant adverse consequences, such as decreased quality of life and increased risk for pouchitis, pouch failure, and even pouch neoplasia.”

She added, “One of the things I see clinically is that if a patient is having bleeding, in addition to urgency and frequency, that is often related to the cuff.” Treatment often involves the use of topical agents, such as 5-ASA or steroid suppository. When patients are refractory to this treatment biologic therapies can be used.

What about novel approaches to managing pouch-related disorders? Dr Long reviewed the potential for the use of fecal microbiotal transplantation (FMT). “Although antibiotics are a mainstay of pouchitis, there is significant interest in other methods for manipulation of the microbiome,” such as FMT. “This is definitely outside the box,” she said, but the pouch may be an appropriate arena for FMT, although initial studies have not demonstrated significant benefit.

Hyperbaric oxygen therapy has several effects that may be helpful in the treatment of IBD, including cuffitis and inflammatory conditions of the pouch, Dr Long said. “It increases the oxygen content of blood reaching inflamed bowel or nonhealing fistulas, it alters signaling pathways in the tissue response to hypoxia and wound repair, and it suppresses the production of proinflammatory cytokines and chemokines,” she explained.

A retrospective study of 46 patients with a mix of inflammatory conditions of the pouch found that after 10 to 60 sessions, the median baseline modified Pouchitis Disease Activity Index score was 9.77, which decreased to 5.44 after treatment with hyperbaric oxygen therapy. “Among 24 patients with a fistula, 54% had complete healing and 29% showed some partial improvement.”

Literature to guide dietary recommendations for patients with pouch complications is limited, Dr Long said. In general, patients are advised to avoid foods that loosen stool consistency or increase gas production and to favor foods that thicken the stool.

“While antibiotics are first-line for chronic inflammatory pouch disorders, advanced therapies are often required for management, with limited clinical trial data,” Dr Long concluded. “Future research efforts using standardized methods may improve our ability to identify at-risk patients and offer earlier, tailored interventions.”

—Rebecca Mashaw

Long M. Pouch Disorders. Presented at: Advances in Inflammatory Bowel Diseases. Virtual.