March 26, 2024
The objectives of this presentation were to examine how to diagnose pouch disorders, explore how to manage acute and chronic pouchitis, and discuss when to refer to a surgeon. A recent review suggests pouchitis is common, with a cumulative probability of 20% at 1 year after pouch formation and up to 40% at 5 years.1 Meanwhile, data from the UK ileoanal pouch registry speak to the importance of optimizing surgical outcomes in an effort to ‘get it right from the start’. The registry included 5352 patients from 2012–17 and found a complication rate of 23% and a failure rate of 5%. Remarkably, the average number of ileal pouch-anal anastomoses (IPAA) performed per surgeon was 3 per year, and 25% of surgeons had performed just 1 IPAA in the last 5 years. These low volume surgeons had higher rates of complications and failures underscoring the importance of referring patients to surgeons with appropriate experience and clinical volume.2
Pouch dysfunction can be due to many reasons beyond pouchitis such as, inflammatory causes (e.g., Crohn’s disease), mechanical causes (e.g., small reservoir), functional causes (e.g., evacuation disorder), or other causes (e.g. bacterial overgrowth).3 Therefore, it is important to carefully assess the cause of pouch dysfunction, taking into consideration the initial indication for surgery, type of pouch and anastomosis, histopathology of the colectomy specimen, presence of extra-intestinal manifestations, history of bowel symptoms, previous pouch function and symptoms, potential GI infection, and current medications.3 Given the range of causes, assessment of pouch dysfunction can involve many types of assessments, as illustrated in Figure 1, including physical examination, blood and stool tests, pouchoscopy, etc., noting that some of these assessments are only needed for specific clinical situations. A retrospective study on the management of patients with pouch dysfunction (n=121), found that the most frequent causes of pouchitis were anastomotic leakage (21%), primary idiopathic pouchitis (20%), and functional disorders (20%).4 However, identifying the cause can be challenging because symptoms, endoscopy, and histology often do not correlate, patients can present with multiple causes of pouchitis, and there is a lack of training in performing and reporting pouchoscopies.
The Pouch Disease Activity Index (PDAI) is an 18-point assessment tool that includes histologic, clinical, and endoscopic criteria, while the modified PDAI (mPDAI), is a shorter 12-point assessment, that excludes histology, while maintaining its diagnostic specificity and sensitivity.5 Recently, the Atlantic Pouchitis Index (API) was developed, which applies the Simple Endoscopic Score-Crohn’s Disease (SES-CD) to pouch endoscopy as a single segment. Data have shown that the correlation with the Visual Analogue Scale (VAS) was better using the SES-CD than the PDAI, however, the API excludes clinical symptoms.6,7
The classification of subtypes of pouchitis is rather arbitrary and can be based on symptom duration, symptom pattern, and/or response to antibiotics, as shown in Table 1.
The European Crohn’s and Colitis Organisation (ECCO) guidelines state that the majority of patients respond to metronidazole or ciprofloxacin, and that side effects are less frequent with ciprofloxacin monotherapy. Antidiarrheal drugs may be added to reduce the number of daily liquid stools. Similarly, the British Society of Gastroenterology (BSG) guidelines recommend a 2-week course of ciprofloxacin or metronidazole, noting that ciprofloxacin is better tolerated and may be more effective than metronidazole.8,9
Around 60% of patients with acute pouchitis develop at least one recurrence and up to 19% develop chronic pouchitis that is refractory to antibiotics.10,11 There are 2 meta-analyses of biologics to treat chronic antibiotic refractory pouchitis (CARP). One included 15 studies (311 patients) of which one was a randomized controlled trial. The pooled rate of clinical remission were 65.7%, 31%, and 47.4% with infliximab, adalimumab, and vedolizumab, respectively.12 The other meta-analysis included 26 studies (741 patients), with a variety of conditions pooled together (CARP/Crohn’s/cuffitis) and looked at clinical response as the endpoint. For the subgroup of patients with chronic pouchitis, it found clinical response rates of 51%, 47%, 41%, and 41% with infliximab, adalimumab, vedolizumab, and ustekinumab, respectively.13
The EARNEST trial was the first randomized controlled trial of advanced therapy in chronic pouchitis and investigated the use of intravenous vedolizumab in patients with active CARP after proctocolectomy and IPAA for ulcerative colitis (n=102). The results showed significant differences in favour of vedolizumab over placebo for mPDAI remission rate at week 14 (primary endpoint) and the key secondary efficacy endpoints of mPDAI remission at week 14, mPDAI response at weeks 14 and 34, and PDAI remission at weeks 14 and 34. Furthermore, the rate of sustained remission (remission at both weeks 14 and 34, mPDAI and PDAI) was significantly higher for vedolizumab versus placebo.14 Subsequent assessment of the endoscopic evaluations from 98 patients from the trial showed a greater reduction in ulcerated surface area with vedolizumab versus placebo at weeks 14 and 34, as well as higher rates of SES-CD remission (weeks 14 and 34) and mucosal healing (week 14).15
The evidence for other advanced therapies in the management of chronic pouchitis is limited and mainly anecdotal. Specifically, for Janus kinase inhibitors (JAKi), there are data for tofacitinib from the GETAID TOFA-POUCH study group, which included 12 patients with CARP, of which 4 achieved steroid-free remission at 8 weeks.16 In addition, a case series from MSSM-Chicago of 14 patients with CARP, showed response to tofacitinib in 3 patients at 12 weeks.17 For ustekinumab, investigation is underway as the SOCRATES (Stelara fOr ChRonic AntibioTic rEfractory pouchitiS) study is recruiting subjects.18
In conclusion, Dr. Travis recapped that pouch dysfunction is not the same as pouchitis, therefore it is crucial to do a full assessment as to the cause(s). For acute pouchitis, the recommended first-line treatment is ciprofloxacin, with or without metronidazole, and vedolizumab is recommended for the treatment of chronic pouchitis. When treating patients with pouchitis, it is important to address the psychological burden and to apply a multidisciplinary approach when possible. For pouch dysfunction that is refractory to antibiotics and/or advanced therapies, ensure that all potential causes of pouch dysfunction have been considered and refer for help.
John K. Marshall, MD MSc FRCPC CAGF AGAF
Professor, Department of Medicine
Director, Division of Gastroenterology
McMaster University
Hamilton, ON
Simon Travis, DPhil FRCP
Professor of Clinical Gastroenterology,
Kennedy Institute and Translational Gastroenterology Unit,
University of Oxford,
Oxford, UK
Alain Bitton, MD FRCPC, McGill University, Montreal, QC
Karen I. Kroeker, MD MSc FRCPC, University of Alberta, Edmonton, AB
Cynthia Seow, MBBS (Hons) MSc FRACP, University of Calgary, Calgary, AB
Jennifer Stretton, ACNP MN BScN, St. Joseph’s Healthcare, Hamilton, ON
Eytan Wine, MD PhD FRCPC, University of Alberta, Edmonton, AB
IBD Dialogue 2024·Volume 20 is made possible by unrestricted educational grants from…
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