IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus

Bénédicte Caron; Maria T Abreu; Corey A Siegel; Remo Panaccione; Bruce E Sands; Axel Dignass; Dan Turner; Iris Dotan; Ailsa L Hart; Vineet Ahuja; Matthieu Allez; Ashwin N Ananthakrishnan; Subrata Ghosh; Anne M Griffiths; Jonas Halfvarson; Arthur Kaser; Paulo G Kotze; Ioannis E Koutroubakis; Peter L Lakatos; Arie Levine; James D Lewis; Fernando Magro; Gerassimos J Mantzaris; Colm O'Morain; Zhihua Ran; Walter Reinisch; Gerhard Rogler; David B Sachar; Britta Siegmund; Mark S Silverberg; Ajit Sood; Antonino Spinelli; Flavio Steinwurz; Curt Tysk; Jesus K Yamamoto-Furusho; Stefan Schreiber; David T Rubin; William J Sandborn; Silvio Danese; Laurent Peyrin-Biroulet

doi:10.1016/j.cgh.2022.02.032

IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus

Clin Gastroenterol Hepatol. 2022 Nov;20(11):2619-2627.e1. doi: 10.1016/j.cgh.2022.02.032. Epub 2022 Feb 19.

Authors

Bénédicte Caron¹, Maria T Abreu², Corey A Siegel³, Remo Panaccione⁴, Bruce E Sands⁵, Axel Dignass⁶, Dan Turner⁷, Iris Dotan⁸, Ailsa L Hart⁹, Vineet Ahuja¹⁰, Matthieu Allez¹¹, Ashwin N Ananthakrishnan¹², Subrata Ghosh¹³, Anne M Griffiths¹⁴, Jonas Halfvarson¹⁵, Arthur Kaser¹⁶, Paulo G Kotze¹⁷, Ioannis E Koutroubakis¹⁸, Peter L Lakatos¹⁹, Arie Levine²⁰, James D Lewis²¹, Fernando Magro²², Gerassimos J Mantzaris²³, Colm O'Morain²⁴, Zhihua Ran²⁵, Walter Reinisch²⁶, Gerhard Rogler²⁷, David B Sachar²⁸, Britta Siegmund²⁹, Mark S Silverberg³⁰, Ajit Sood³¹, Antonino Spinelli³², Flavio Steinwurz³³, Curt Tysk¹⁵, Jesus K Yamamoto-Furusho³⁴, Stefan Schreiber³⁵, David T Rubin³⁶, William J Sandborn³⁷, Silvio Danese³⁸, Laurent Peyrin-Biroulet³⁹

Affiliations

¹ Nancy University Hospital, Department of Gastroenterology and University of Lorraine, Inserm, Nutrition-Génétique et Exposition aux Risques Environnementaux, F-54000 Nancy, France.
² Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
³ Inflammatory Bowel Disease Center, Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
⁴ Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada.
⁵ Dr. Henry D. Janowitz Division of Gastroenterology.
⁶ Department of Medicine I, Agaplesion Markus Hospital, Goethe-University, Frankfurt am Main, Germany.
⁷ Juliet Keidan Institute of Pediatric Gastroenterology Hepatology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
⁸ Division of Gastroenterology, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁹ Inflammatory Bowel Disease Unit, St. Mark's Hospital, Harrow, United Kingdom.
¹⁰ Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
¹¹ Department of Gastroenterology, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris, INSERM U1160, Université de Paris, Paris, Île-de-France, France.
¹² Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
¹³ College of Medicine and Health, University College Cork, Cork, Ireland.
¹⁴ SickKids Inflammatory Bowel Disease Center, Division of Gastroenterology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
¹⁵ Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
¹⁶ University of Cambridge, Cambridge University Hospitals-Addenbrooke's Hospital, Cambridge, United Kingdom.
¹⁷ Inflammatory Bowel Disease Outpatient Clinics, Colorectal Surgery Unit, Catholic University of Paraná, Curitiba, Brazil.
¹⁸ Department of Gastroenterology, University Hospital of Heraklion, Medical School, University of Crete, Crete, Greece.
¹⁹ Department of Medicine and Oncology, Semmelweis University, McGill University Health Center, Montreal General Hospital, Montreal, Canada.
²⁰ Pediatric Gastroenterology Unit, Paediatric Inflammatory Bowel Diseases Research Center, Wolfson Medical Center, Holon, Israel.
²¹ Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
²² Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Clinical Pharmacology, São João University Hospital Center (CHUSJ), Porto, Portugal; Faculty of Medicine, University of Porto, Portugal. Center for Health Technology and Services Research (CINTESIS), Porto, Portugal; Center for Health Technology and Services Research (CINTESIS), Porto, Portugal.
²³ Department of Gastroenterology, Evangelismos-Polykliniki General Hospital, Athens, Greece.
²⁴ Faculty of Health Sciences, University of Dublin, Trinity College, Dublin, Ireland.
²⁵ Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
²⁶ Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
²⁷ Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
²⁸ Chief Emeritus of Gastroenterology and Professor of Medicine, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
²⁹ Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Department of Gastroenterology, Rheumatology and Infectious Disease, Campus Benjamin Franklin, Berlin, Germany.
³⁰ Mount Sinai Hospital Inflammatory Bowel Disease Centre, Toronto, Ontario, Canada.
³¹ Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiāna, Punjab, India.
³² Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Division of Colon and Rectal Surgery, Scientific Institute for Research, Hospitalization and Healthcare Humanitas Research Hospital, Rozzano, Milan, Italy.
³³ Department of Gastroenterology, Albert Einstein Israelite Hospital, São Paulo, Brazil.
³⁴ Inflammatory Bowel Disease Clinic, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpa, Mexico.
³⁵ Department of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.
³⁶ Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Illinois.
³⁷ Division of Gastroenterology, University of California San Diego, La Jolla, California.
³⁸ Humanitas Research Hospital, University Vita-Salute San Raffaele, Milano, Italy.
³⁹ Nancy University Hospital, Department of Gastroenterology and University of Lorraine, Inserm, Nutrition-Génétique et Exposition aux Risques Environnementaux, F-54000 Nancy, France. Electronic address: peyrinbiroulet@gmail.com.

PMID: 35189386
DOI: 10.1016/j.cgh.2022.02.032

Abstract

Background & aims: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults.

Methods: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters.

Results: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life.

Conclusions: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.

Keywords: Consensus; Definition; Endpoint; Ulcerative Proctitis.

Publication types

Review

MeSH terms

Adult
Colitis, Ulcerative* / drug therapy
Colitis, Ulcerative* / therapy
Crohn Disease* / drug therapy
Endoscopy
Humans
Proctitis* / diagnosis
Proctitis* / drug therapy
Quality of Life