An International Consensus to Standardize Integration of Histopathology in Ulcerative Colitis Clinical Trials

Christopher Ma; Rocio Sedano; Ahmed Almradi; Niels Vande Casteele; Claire E Parker; Leonardo Guizzetti; David F Schaeffer; Robert H Riddell; Reetesh K Pai; Robert Battat; Bruce E Sands; Christophe Rosty; Marla C Dubinsky; Florian Rieder; Noam Harpaz; Maria T Abreu; Robert V Bryant; Gregory Y Lauwers; Richard Kirsch; Mark A Valasek; Eileen Crowley; William J Sandborn; Brian G Feagan; Rish K Pai; Vipul Jairath

doi:10.1053/j.gastro.2021.02.035

An International Consensus to Standardize Integration of Histopathology in Ulcerative Colitis Clinical Trials

Gastroenterology. 2021 Jun;160(7):2291-2302. doi: 10.1053/j.gastro.2021.02.035. Epub 2021 Feb 19.

Authors

Christopher Ma¹, Rocio Sedano², Ahmed Almradi², Niels Vande Casteele³, Claire E Parker⁴, Leonardo Guizzetti⁴, David F Schaeffer⁵, Robert H Riddell⁶, Reetesh K Pai⁷, Robert Battat⁸, Bruce E Sands⁹, Christophe Rosty¹⁰, Marla C Dubinsky¹¹, Florian Rieder¹², Noam Harpaz¹³, Maria T Abreu¹⁴, Robert V Bryant¹⁵, Gregory Y Lauwers¹⁶, Richard Kirsch⁶, Mark A Valasek¹⁷, Eileen Crowley¹⁸, William J Sandborn³, Brian G Feagan¹⁹, Rish K Pai²⁰, Vipul Jairath¹⁹

Affiliations

¹ Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Alimentiv Inc (formerly Robarts Clinical Trials, Inc), London, Ontario, Canada. Electronic address: christopher.ma@ucalgary.ca.
² Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada.
³ Alimentiv Inc (formerly Robarts Clinical Trials, Inc), London, Ontario, Canada; Division of Gastroenterology, University of California San Diego, La Jolla, California.
⁴ Alimentiv Inc (formerly Robarts Clinical Trials, Inc), London, Ontario, Canada.
⁵ Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
⁶ Department of Laboratory Medicine and Pathobiology, Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute, University of Toronto, Toronto, Ontario, Canada.
⁷ Division of Anatomic Pathology, Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
⁸ Jill Roberts Center for IBD, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York.
⁹ Department of Medicine, The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York.
¹⁰ Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Envoi Pathology, Brisbane, Queensland, Australia.
¹¹ Department of Pediatrics, Division of Pediatric Gastroenterology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York.
¹² Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
¹³ Department of Medicine, The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York; Department of Pathology, Molecular and Cell-Based Medicine and Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
¹⁴ Crohn's and Colitis Center, Division of Gastroenterology, Department of Medicine, University of Miami Leonard Miller School of Medicine, Miami, Florida.
¹⁵ Inflammatory Bowel Disease Service, Department of Gastroenterology, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; Faculty of Health Sciences, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
¹⁶ D.H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida.
¹⁷ Department of Pathology, University of California San Diego, La Jolla, California.
¹⁸ Division of Pediatric Gastroenterology, Western University, Children's Hospital, London Health Sciences Centre, London, Ontario, Canada.
¹⁹ Alimentiv Inc (formerly Robarts Clinical Trials, Inc), London, Ontario, Canada; Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
²⁰ Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona.

Abstract

Background & aims: Histopathology is an emerging treatment target in ulcerative colitis (UC) clinical trials. Our aim was to provide guidance on standardizing biopsy collection protocols, identifying optimal evaluative indices, and defining thresholds for histologic response and remission after treatment.

Methods: An international, interdisciplinary expert panel of 19 gastroenterologists and gastrointestinal pathologists was assembled. A modified RAND/University of California, Los Angeles appropriateness methodology was used to address relevant issues. A total of 138 statements were derived from a systematic review of the literature and expert opinion. Each statement was anonymously rated as appropriate, uncertain, or inappropriate using a 9-point scale. Survey results were reviewed and discussed before a second round of voting.

Results: Histologic measurements collected using a uniform biopsy strategy are important for assessing disease activity and determining therapeutic efficacy in UC clinical trials. Multiple biopsy strategies were deemed acceptable, including segmental biopsies collected according to the endoscopic appearance. Biopsies should be scored for architectural change, lamina propria chronic inflammation, basal plasmacytosis, lamina propria and epithelial neutrophils, epithelial damage, and erosions/ulcerations. The Geboes score, Robarts Histopathology Index, and Nancy Index were considered appropriate for assessing histologic activity; use of the modified Riley score and Harpaz Index were uncertain. Histologic activity at baseline should be required for enrollment, recognizing this carries operational implications. Achievement of histologic improvement or remission was considered an appropriate and realistic therapeutic target. Current histologic indices require validation for pediatric populations.

Conclusions: These recommendations provide a framework for standardized implementation of histopathology in UC trials. Additional work is required to address operational considerations and areas of uncertainty.

Keywords: Geboes Score; Histology; Inflammatory Bowel Disease; Nancy Index; Robarts Histopathology Index.

MeSH terms

Biopsy / standards*
Clinical Trials as Topic / standards*
Colitis, Ulcerative*
Consensus
Gastroenterology / standards*
Humans
Pathology, Clinical / standards*
Reference Standards
Remission Induction

Abstract

MeSH terms

Grants and funding