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

• Published in: Alimentary pharmacology & therapeutics 2021-05, Vol.53 (10), p.1108-1117
• Main Authors: Sedano, Rocio, Ma, Christopher, Pai, Rish K., D' Haens, Geert, Guizzetti, Leonardo, Shackelton, Lisa M., Remillard, Julie, Gionchetti, Paolo, Gordon, Ilyssa O., Holubar, Stefan, Kayal, Maia, Lauwers, Gregory Y., Pai, Reetesh K., Pardi, Darrell S., Samaan, Mark A., Schaeffer, David F., Shen, Bo, Silverberg, Mark S., Feagan, Brian G., Sandborn, William J., Jairath, Vipul
• Format: Article
• Language: English
• Subjects: Clinical trials; Drug development; Endoscopy; Feces; Inflammation; Lamina propria; Leukocytes (neutrophilic); Remission; Ulcers
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/apt.16328

Summary Background Pouchitis 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. Aim To conduct a modified RAND/University of California Los Angeles appropriateness process to produce a standardised assessment of pouchitis disease activity in clinical trials. Methods A 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. Results Items 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 (75%), evaluation of the presence of ulcers/erosions according to size (erosions 2 cm) and ulcerated area (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’. Conclusion We conducted a RAND/UCLA appropriateness process to help inform measurement of pouchitis disease activity within clinical trials and foster the development of novel therapies. The lack of validated instruments for measuring pouchitis disease activity is a barrier to drug development. A panel of 16 expert gastroenterologists, subspecialty gastroenterology pathologists and surgeons was assembled and participated in a two‐round consensus process using modified RAND/UCLA appropriateness methodology to standardise clinical, endoscopic and histologic assessment of pouchitis disease activity, as well as the configuration of clinical trial inclusion criteria and outcome definitions.