Gastroenterology. 2022 Oct;163(4):950-964. doi: 10.1053/j.gastro.2022.06.068.Epub 2022 Jul 3.

CORE-IBD Collaborators; Christopher Ma ¹, Jurij Hanzel ², Remo Panaccione ³, William J Sandborn ⁴, Geert R D'Haens ⁵, Vineet Ahuja ⁶, Raja Atreya ⁷, Charles N Bernstein ⁸, Peter Bossuyt ⁹, Brian Bressler ¹⁰, Robert V Bryant ¹¹, Benjamin Cohen ¹², Jean-Frederic Colombel ¹³, Silvio Danese ¹⁴, Axel Dignass ¹⁵, Marla C Dubinsky ¹⁶, Phillip R Fleshner ¹⁷, Richard B Gearry ¹⁸, Stephen B Hanauer ¹⁹, Ailsa Hart ²⁰, Paulo Gustavo Kotze ²¹, Torsten Kucharzik ²², Peter L Lakatos ²³, Rupert W Leong ²⁴, Fernando Magro ²⁵, Julian Panés ²⁶, Laurent Peyrin-Biroulet ²⁷, Zhihua Ran ²⁸, Miguel Regueiro ¹², Siddharth Singh ²⁹, Antonino Spinelli ³⁰, A Hillary Steinhart ³¹, Simon P Travis ³², C Janneke van der Woude ³³, Bruce Yacyshyn ³⁴, Takayuki Yamamoto ³⁵, Matthieu Allez ³⁶, Willem A Bemelman ³⁷, Amy L Lightner ³⁸, Edouard Louis ³⁹, David T Rubin ⁴⁰, Ellen J Scherl ⁴¹, Corey A Siegel ⁴², Mark S Silverberg ⁴³, Severine Vermeire ⁴⁴, Claire E Parker ⁴⁵, Stefanie C McFarlane ⁴⁵, Leonardo Guizzetti ⁴⁵, Michelle I Smith ⁴⁵, Niels Vande Casteele ⁴, Brian G Feagan ⁴⁶, Vipul Jairath ⁴⁷

Author information

¹Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Alimentiv Inc, London, Ontario, Canada. Electronic address: christopher.ma@ucalgary.ca.

²Alimentiv Inc, London, Ontario, Canada; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Department of Gastroenterology, University Medical Center Ljubljana, Ljubljana, Slovenia.

³Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada.

⁴Division of Gastroenterology, University of California San Diego, La Jolla, California.

⁵Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

⁶Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

⁷Medical Department I, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

⁸Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, Winnipeg, Manitoba, Canada.

⁹Imelda Gastrointestinal Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium.

¹⁰Department of Medicine, Division of Gastroenterology, St Paul's Hospital, University of British Columbia, British Columbia, Canada.

¹¹Inflammatory Bowel Disease Service, Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; School of Medicine, Faculty of Health Sciences University of Adelaide, Adelaide, South Australia, Australia.

¹²Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio.

¹³Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.

¹⁴Department of Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, Milan, Italy; Department of Gastroenterology and Endoscopy, San Raffaele Hospital, Milan, Italy.

¹⁵Department of Medicine I, Agaplesion Markus Hospital, Goethe-University, Frankfurt am Main, Germany.

¹⁶Department of Pediatrics, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.

¹⁷Division of Colorectal Surgery, Cedars-Sinai Medical Center, Los Angeles, California.

¹⁸Department of Medicine, University of Otago, Christchurch, New Zealand.

¹⁹Department of Medicine (Gastroenterology and Hepatology), Northwestern University, Chicago, Illinois.

²⁰Department of Gastroenterology, St Mark's Hospital and Academic Institute, Harrow, United Kingdom.

²¹Inflammatory Bowel Disease Outpatient Clinics, Colorectal Surgery Unit, Pontificia Universidade Catolica do Paraná, Curitiba, Brazil.

²²Department of Gastroenterology, Lüneburg Hospital, University of Hamburg, Lüneburg, Germany.

²³Division of Gastroenterology, McGill University, Montreal, Canada; 1st Department of Medicine, Semmelweis University, Budapest, Hungary.

²⁴The University of Sydney, Sydney, New South Wales, Australia; Concord Repatriation General Hospital, Sydney, New South Wales, Australia.

²⁵Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Clinical Pharmacology, São João University Hospital Center, Porto, Portugal; Faculty of Medicine, University of Porto, Portugal; Center for Health Technology and Services Research, Porto, Portugal.

²⁶Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute, Biomedical Research Networking Center in Hepatic and Digestive Disease, Barcelona, Spain.

²⁷Department of Gastroenterology, INSERM NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France.

²⁸Division 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.

²⁹Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California.

³⁰Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Istituto di Ricovero e Cura a Carattere Scientifico, Humanitas Research Hospital, Rozzano, Milan, Italy.

³¹Mount Sinai Hospital Inflammatory Bowel Disease Centre, Toronto, Ontario, Canada; Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

³²Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom.

³³Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.

³⁴Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio.

³⁵Inflammatory Bowel Disease Center and Department of Surgery, Yokkaichi Hazu Medical Center, Yokkaichi, Japan.

³⁶Department of Gastroenterology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, INSERM U1160, Université de Paris, Paris, Île-de-France, France.

³⁷Department of Surgery, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

³⁸Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio.

³⁹Hepato-Gastroenterology and Digestive Oncology Department, University and Centre Hospitalier Universitaire Liège, Liège, Belgium.

⁴⁰University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, Illinois.

⁴¹Jill Roberts Center for Inflammatory Bowel Disease, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York.

⁴²Inflammatory Bowel Disease Center, Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.

⁴³Mount Sinai Hospital Inflammatory Bowel Disease Centre, Toronto, Ontario, Canada.

⁴⁴Department of Gastroenterology and Hepatology, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.

⁴⁵Alimentiv Inc, London, Ontario, Canada.

⁴⁶Alimentiv 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.

⁴⁷Alimentiv 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. Electronic address: vjairath@uwo.ca.

Abstract

Background & aims: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease.

Methods: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists.

Results: A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities.

Conclusions: This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC.