An expert consensus to standardise clinical, endoscopic and histologic items and inclusion and outcome criteria for evaluation of pouchitis disease activity in clinical trials

Abstract

SummaryBackgroundPouchitis is a condition with large unmet medical needs and no approved therapies. Lack of validated instruments to measure disease activity and treatment response is a major barrier to drug development.AimTo conduct a modified RAND/University of California Los Angeles appropriateness process to produce a standardised assessment of pouchitis disease activity in clinical trials.MethodsA list of 164 items generated upon a systematic review and expert opinion were rated based on a 9‐point scale (appropriate, uncertain and inappropriate), by a panel including 16 gastroenterologists, surgeons and histopathologists.ResultsItems rated as appropriate to evaluate in pouchitis clinical trials were: (a) clinical: stool frequency and faecal urgency; (b) endoscopic: primary assessment in the pouch body according to the percentage of affected area (<50%, 50%‐75% and >75%), evaluation of the presence of ulcers/erosions according to size (erosions <5 mm, ulcers ≥5 mm to 2 cm and large ulcers >2 cm) and ulcerated area (<10%, 10%‐30% and >30%); (c) histologic: two biopsies from each segment, from the ulcer's edge when present, or endoscopically normal areas, assessment of lamina propria chronic inflammation, epithelial and lamina propria neutrophils, epithelial damage, erosions and ulcers; and (d) clinical trial inclusion/outcome criteria: minimum histologic disease activity for inclusion, a primary endpoint based on stool frequency and assessment of clinical, endoscopic and histologic response and remission. The overall majority of items surveyed (100/164) were rated ‘uncertain’.ConclusionWe conducted a RAND/UCLA appropriateness process to help inform measurement of pouchitis disease activity within clinical trials and foster the development of novel therapies.

Effectiveness and safety of azathioprine for inflammatory pouch disorders: results from the RESERVO study of GETECCU

“…A recent expert consensus group used a RAND/UCLA process to help clinicians and investigators assess the activity of pouchitis based on clinical factors such as stool frequency, faecal urgency and endoscopic and histological activity. 40 In our cohort, 19 patients (30%) were also evaluated using endoscopy, which revealed a decrease in the PDAI sub-score. On the other hand, ours is the first publication to date to report the effectiveness of azathioprine in inflammatory pouch disorders and to include a relevant number of patients belonging to a large multicentre and nationwide cohort affected by a rare condition within IBD.…”

Endoscopic Evaluation of the Ileal Pouch

“…A consensus panel of 16 experts suggested the following items to be included in clinical trials: 1) clinical assessment: stool frequency and fecal urgency; 2) endoscopy: primary assessment in the pouch body according to the percentage of affected area (<50%, 50%–75%, and >75%), evaluation of the presence of ulcers/erosions according to size (erosions <5 mm, ulcers ≥5 mm–2 cm, and large ulcers >2 cm), and ulcerated area (<10%, 10%–30%, and >30%); 3) histology: 2 biopsies from each segment, from the ulcer’s edge when present, or endoscopically normal areas, as well as assessment of lamina propria chronic inflammation, epithelial and lamina propria neutrophils, epithelial damage, erosions, and ulcers. 54…”