ClinGastroenterolHepatol. 2024Dec14:S15423565(24)010826.doi:10.1016/j.cgh.2024.10.029. Online ahead of print.

Sailish Honap ¹, Vipul Jairath ², Bruce E Sands ³, Parambir S Dulai ⁴, Peter Dr Higgins ⁵, Peter De Cruz ⁶, Ana Gutiérrez ⁷, Paulo G Kotze ⁸, Byong Duk Ye ⁹, Taku Kobayashi ¹⁰, Richard B Gearry ¹¹, Pablo A Olivera ¹², Aurélien Amiot ¹³, Mahmoud H Mosli ¹⁴, Sameer Al Awadhi ¹⁵, Jonas Halfvarson ¹⁶, Kamal V Patel ¹⁷, Shaji Sebastian ¹⁸, Silvio Danese ¹⁹, Laurent Peyrin-Biroulet ²⁰

Author information

¹INFINY Institute, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France; Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK; School of Immunology and Microbial Sciences, King's College London, UK. Electronic address: sailish.honap@kcl.ac.uk.

²Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University, London, ON, Canada; Lawson Health Research Institute, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.

³Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

⁴Division of Gastroenterology, Northwestern University, Chicago, Illinois, USA.

⁵Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan, USA.

⁶Department of Gastroenterology, Austin Health, Melbourne, Australia; Department of Medicine (Austin Health), The University of Melbourne, Melbourne, Australia.

⁷Department of Gastroenterology, Hospital General Universitario Dr Balmis de Alicante, Alicante, Spain; Instituto de Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.

⁸Colorectal Surgery Unit, Pontificia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil.

⁹Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

¹⁰Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.

¹¹Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand; Department of Gastroenterology, Christchurch Hospital, New Zealand.

¹²IBD Unit, Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigación Clínica (CEMIC), Buenos Aires, Argentina; Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.

¹³Department of Gastroenterology, Hôpitaux Universitaires Bicêtre, AP-HP, Université Paris Saclay, Le Kremlin Bicêtre, France; Centre for Epidemiology and Population Health, INSERM, Universite Paris Saclay, Villejuif, France.

¹⁴Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

¹⁵Digestive Diseases Unit, Rashid Hospital, Dubai, United Arab Emirates.

¹⁶Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.

¹⁷Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK.

¹⁸IBD Unit, Department of Gastroenterology, Hull University Teaching Hospitals, Hull, UK.

¹⁹Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy.

²⁰Université de Lorraine, CHRU, Inserm, INFINY Institute, NGERE, F-54000 Nancy, France.

Abstract

Background & aims: Interventional clinical trials in ASUC are characterised by substantial heterogeneity due to a lack of consensus in several key areas of trial design - this impedes clinical research efforts to identify novel therapies. The objective of this initiative was to achieve the first consensus and provide clear position statements on ASUC trial design.

Methods: A modified Delphi consensus approach was employed with a panel of twenty clinicians with international representation and expertise in ASUC trial design and delivery. Agreement was defined as at least 75% of participants voting as 'agree' with each statement.

Results: In total, thirty statements achieved consensus and were approved. Statements centred on proposing suitable eligibility criteria (disease extent, disease severity, prior therapy exposure), optimising trial design (randomisation, stratification, corticosteroid handling, timing of assessments), and recommending primary and secondary endpoints alongside defining key efficacy outcomes (clinical and endoscopic reponse and remission, treatment failure, quality of life).

Conclusions: The expansion of drugs to treat moderate-severe UC over the past decade, particularly the rapidly acting Janus kinase inhibitors, is promising and has reignited the interest in identifying suitable therapeutic candidates for ASUC. Clinical trials in this high-risk population are challenging to conduct and this consensus provides a framework for future trials to advance drug development.