Management of Pouchitis and Inflammatory Pouch Disorders

• Normal bowel function after IPAA for UC and typical symptoms of pouchitis: After an initial period of postoperative adjustment, patients can expect to average 4–8 bowel movements per day and 1–2 bowel movements per night. A variety of clinical symptoms have been described in patients with pouchitis; typical symptoms are increased stool frequency, urgency, abdominal pain or cramping, or pelvic discomfort. Clinical symptoms of pouchitis do not necessarily correlate with findings on endoscopy or histology.
• Endoscopic evaluation in patients with pouch disorders: Pouchoscopy should be performed in patients experiencing frequent recurrent episodes of pouchitis (suspected chronic antibiotic-dependent pouchitis), in patients with inadequate response to antibiotics before considering other therapies (suspected chronic antibiotic-refractory pouchitis), in patients experiencing atypical symptoms of pouchitis, and when the diagnosis of Crohn’s-like disease of the pouch is being considered. Routine pouchoscopy to confirm pouch inflammation in patients experiencing typical symptoms of pouchitis, before initiation of antibiotics, or in patients who experience infrequent episodes of pouchitis that respond to typical management, may not be required, although it may provide additional information on disease severity in this setting.
• Treatment goals and targets in patients with pouch disorders: The overall goal of treating patients with pouchitis is resolution of symptoms. Endoscopic and/or histologic resolution of inflammation was not considered a critical treatment goal at this time due to lack of data on the additional benefits of achieving these goals. By extension, asymptomatic patients who have endoscopic evidence of inflammation of the pouch may not routinely warrant treatment.
• Alternative etiologies for patients with pouch disorders: In patients with atypical symptoms of pouchitis or with inadequate response to conventional therapy or recurrent symptoms of pouchitis, alternative etiologies of symptoms should be considered. These include Clostridioides difficile infection of the pouch; mechanical obstructions, such as strictures at the ileo-anal anastomosis or the pouch inlet or stoma takedown site (approximately 20–40 cm proximal to pouch inlet), and nonrelaxing pelvic floor dysfunction.

• Intermittent pouchitis
  • Isolated and infrequent episodes of typical pouchitis symptoms that resolve with therapy (most commonly antibiotics) or spontaneously, followed by extended periods of normal pouch function (typically months to years). Because antibiotics are the most commonly used therapy for symptoms of pouchitis, we anchored our functional definitions of pouchitis around response to antibiotic therapy.
• Chronic antibiotic-dependent pouchitis
  • Recurrent episodes of pouchitis that responds to antibiotic therapy but relapses shortly after stopping antibiotics (typically within days to weeks), and often requires recurrent or continuous antibiotic therapy or other advanced therapies to achieve symptom control. We did not define this entity on the basis of a specific number of pouchitis episodes within a 12-month time period because this is a continuum (some patients may require 3–4 courses of antibiotics per year and others require almost continuous antibiotics) and patients’ and providers’ preferences for treatment approach vary depending on frequency of these episodes.
• Chronic antibiotic-refractory pouchitis
  • Relapsing–remitting or continuous symptoms of pouchitis with inadequate response to typical antibiotic therapy (ongoing symptoms attributable to pouchitis), often needing escalation to other therapies
• Crohn’s-like disease of the pouch
  • Defined on the basis of the most common and accepted diagnostic criteria for this condition, recognizing variability in prior literature. These diagnostic criteria include presence of a perianal or other fistula that developed at least 12 months after the final stage of IPAA surgery, stricture of the pouch body or prepouch ileum, and the presence of prepouch ileitis. The panel recognized that pouchitis may often coexist in patients with Crohn’s-like disease of the pouch.

Comment: There is a need for better evidence from clinical trials to inform the use of probiotics as a primary prevention strategy for pouchitis, especially given the potential cost and burden of long-term use with limited data on potential benefits.

Comment: There is a need for better evidence from clinical trials to inform the use of antibiotics as a primary prevention strategy for pouchitis, especially given the potential adverse effects and burden of long-term use with limited data on potential benefits.

• Based on available evidence, ciprofloxacin and/or metronidazole are the preferred antibiotics for treatment of pouchitis.
• The typical duration of antibiotic therapy for the treatment of pouchitis is 2–4 weeks.
• An approach using a combination of antibiotics may be more effective in patients who do not respond to single-antibiotic therapy.
• Alternative antibiotic regimens, such as oral vancomycin, may be considered in patients who do not respond to the initial course of antibiotics or have allergies or intolerance to ciprofloxacin and/or metronidazole.

Comment: Patients, particularly those with infrequent episodes of recurrent pouchitis or when the burden of long-term probiotic treatment is excessive, may reasonably choose avoiding any treatment to prevent recurrence of pouchitis.

Implementation consideration:

• De Simone formulation of multistrain probiotics was used in clinical trials of prevention of pouchitis.

Implementation considerations

• The panel suggests endoscopic evaluation of the pouch with confirmation of inflammation and ruling out alternative etiologies in patients with recurrent pouchitis.
• Lowest effective dose of antibiotics (eg, ciprofloxacin 500 mg daily or 250 mg twice daily) with intermittent gap periods (such as approximately 1 week per month), or use of cyclical antibiotics (such as rotating between ciprofloxacin, metronidazole, and vancomycin every 1–2 weeks) may be considered to decrease risk of antimicrobial resistance.

Implementation considerations

• The panel suggests endoscopic evaluation of the pouch with confirmation of inflammation and ruling out alternative etiologies in patients with recurrent pouchitis.
• Advanced immunosuppressive therapies approved for treatment of UC or Crohn's disease (CD) may be used, including TNF–α antagonists (ie, infliximab, adalimumab, golimumab, certolizumab pegol), ustekinumab, risankizumab, ozanimod, tofacitinib, and upadacitinib.
• Advanced immunosuppressive therapies may be used in lieu of chronic, continuous antibiotic therapy, particularly in patients who are intolerant to antibiotics or when patients and/or providers are concerned about risks of long-term antibiotic therapy.
• Advanced immunosuppressive therapies that patients have used before colectomy may be reconsidered.

Implementation consideration:

• The panel suggests endoscopic evaluation of the pouch with confirmation of inflammation and ruling out alternative etiologies in patients with recurrent pouchitis.
• Immunosuppressive therapies approved for treatment of UC or CD may be used, including TNF-α antagonists (ie, infliximab, adalimumab, golimumab, certolizumab pegol), vedolizumab, ustekinumab, risankizumab, ozanimod, tofacitinib, and upadacitinib.
• Vedolizumab is the only advanced therapy to date that has received regulatory approval from the European Medicines Agency for this indication.
• Advanced therapies that patients have used before colectomy may be reconsidered.
• A subset of patients may continue to derive partial symptomatic benefit from antibiotics and may benefit from ongoing use of antibiotics besides advanced immunosuppressive therapies.

Implementation considerations

• Controlled ileal-release budesonide is the preferred corticosteroid formulation.
• Corticosteroids should generally be used for a short duration (<8–12 weeks) with consideration of steroid-sparing therapies for long-term use.
• The panel suggests endoscopic evaluation of the pouch with confirmation of inflammation and ruling out alternative etiologies in patients with recurrent pouchitis.

• Although sulfasalazine may be effective in patients with infrequent episodes of pouchitis, its effectiveness in patients with chronic antibiotic-refractory pouchitis is unknown.

Implementation considerations

• Controlled ileal-release budesonide is the preferred corticosteroid formulation.
• Corticosteroids should generally be used for a short duration (<8 weeks) with consideration of steroid-sparing therapies for long-term use.
• The panel suggests endoscopic evaluation of the pouch to confirm Crohn’s-like disease of the pouch.

• Immunosuppressive therapies approved for treatment of UC or CD may be used, including TNF-α antagonists (ie, infliximab, adalimumab, golimumab, and certolizumab pegol), vedolizumab, ustekinumab, risankizumab, ozanimod, tofacitinib, and upadacitinib.
• Advanced therapies that patients have used before colectomy may be reconsidered.
• A subset of patients may continue to require chronic antibiotics for associated pouchitis and ongoing symptom management, despite the use of advanced immunosuppressive therapies.
• The panel suggests endoscopic evaluation of the pouch to confirm Crohn’s-like disease of the pouch.

• Controlled ileal-release budesonide is the preferred corticosteroid formulation.
• Corticosteroids should generally be used for a short duration (<8 weeks) with consideration of steroid-sparing therapies for long-term use.
• The panel suggests endoscopic evaluation of the pouch to confirm Crohn’s-like disease of the pouch.

• Immunosuppressive therapies approved for treatment of UC or CD may be used, including TNF-α antagonists (ie, infliximab, adalimumab, golimumab, and certolizumab pegol), vedolizumab, ustekinumab, risankizumab, ozanimod, tofacitinib, and upadacitinib.
• Advanced therapies that patients have used before colectomy may be reconsidered.
• A subset of patients may continue to require chronic antibiotics for associated pouchitis and ongoing symptom management, despite the use of advanced immunosuppressive therapies.
• The panel suggests endoscopic evaluation of the pouch to confirm Crohn’s-like disease of the pouch.

• In patients with cuffitis, topical therapies should be the first-line therapy, such as mesalamine suppositories, corticosteroid suppositories, or corticosteroid ointment applied directly to the cuff.
• In patients with refractory cuffitis, immunosuppressive therapies approved for treatment of UC may be used, including TNF-α antagonists (ie, infliximab, adalimumab, golimumab, and certolizumab pegol), vedolizumab, ustekinumab, risankizumab, ozanimod, tofacitinib, and upadacitinib.