Treat-to-target of endoscopic remission in patients with inflammatory bowel disease in symptomatic remission on advanced therapies (QUOTIENT): rationale, design and protocol for an open-label, multicentre, pragmatic, randomised controlled trial

Siddharth Singh; Jasmine D Nguyen; David I Fudman; Mark E Gerich; Samir A Shah; David Hudesman; Ryan A McConnell; Dana J Lukin; Ann D Flynn; Caroline Hwang; Brandon Sprung; Jill K J Gaidos; Mark C Mattar; David T Rubin; Jana G Hashash; Mark Metwally; Tauseef Ali; Christopher Ma; Frank Hoentjen; Neeraj Narula; Talat Bessissow; Greg Rosenfeld; Jeffrey D McCurdy; Ashwin N Ananthakrishnan; Raymond K Cross; Jorge R Rodriguez Gaytan; Emily-Sophinie Gurrola; Sagar Patel; Corey A Siegel; Gil Y Melmed; S Alandra Weaver; Sydney Power; Guangyong Zou; Vipul Jairath; Jason K Hou

doi:10.1136/bmjgast-2024-001615

Treat-to-target of endoscopic remission in patients with inflammatory bowel disease in symptomatic remission on advanced therapies (QUOTIENT): rationale, design and protocol for an open-label, multicentre, pragmatic, randomised controlled trial

BMJ Open Gastroenterol. 2025 Mar 31;12(1):e001615. doi: 10.1136/bmjgast-2024-001615.

Authors

Siddharth Singh^{1

2}, Jasmine D Nguyen³, David I Fudman⁴, Mark E Gerich⁵, Samir A Shah⁶, David Hudesman⁷, Ryan A McConnell⁸, Dana J Lukin⁹, Ann D Flynn¹⁰, Caroline Hwang¹¹, Brandon Sprung¹², Jill K J Gaidos¹³, Mark C Mattar¹⁴, David T Rubin¹⁵, Jana G Hashash¹⁶, Mark Metwally¹⁷, Tauseef Ali¹⁸, Christopher Ma^{19

20}, Frank Hoentjen²¹, Neeraj Narula²², Talat Bessissow²³, Greg Rosenfeld²⁴, Jeffrey D McCurdy^{25

26}, Ashwin N Ananthakrishnan²⁷, Raymond K Cross²⁸, Jorge R Rodriguez Gaytan²⁹, Emily-Sophinie Gurrola³, Sagar Patel³, Corey A Siegel³⁰, Gil Y Melmed³¹, S Alandra Weaver³², Sydney Power³³, Guangyong Zou^{34

35

36}, Vipul Jairath^{34

35

37}, Jason K Hou^{29

38}

Affiliations

¹ Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, USA sis040@ucsd.edu.
² Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, California, USA.
³ Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
⁴ University of Texas Southwestern, Dallas, Texas, USA.
⁵ Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
⁶ Gastroenterology Associates, Inc, powered by the GI Alliance, Providence, Rhode Island, USA.
⁷ NYU Langone Health, New York, New York, USA.
⁸ Palo Alto Medical Foundation, Palo Alto, California, USA.
⁹ Weill Cornell Medicine, New York, New York, USA.
¹⁰ Division of Gastroenterology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA.
¹¹ Digestive Health Institute, Hoag Memorial Hospital, Irvine/Newport Beach, California, USA.
¹² Division of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, New York, USA.
¹³ Section of Digestive Diseases, Yale University, New Haven, Connecticut, USA.
¹⁴ Division of Gastroenterology, Department of Medicine, MedStar Georgetown University Hospital, Washington, District of Columbia, USA.
¹⁵ MacLean Center for Clinical Medical Ethics, University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois, USA.
¹⁶ Division of Gastroenterology and Hepatology, Mayo Clinic Jacksonville, Jacksonville, Florida, USA.
¹⁷ Saratoga Schenectady Gastroenterology Associates, Burnt Hills, New York, USA.
¹⁸ SSM Health Crohn's and Colitis Center, Oklahoma City, Oklahoma, USA.
¹⁹ Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
²⁰ Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
²¹ Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
²² Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
²³ Division of Gastroenterology, Montreal General Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
²⁴ Department of Medicine, IBD Centre of British Columbia, University of British Columbia, Vancouver, British Columbia, Canada.
²⁵ Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
²⁶ Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada.
²⁷ Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.
²⁸ Center for Inflammatory Bowel and Colorectal Diseases, Melissa L. Posner Institute for Digestive Health & Liver Disease at Mercy Medical Center, Baltimore, Maryland, USA.
²⁹ Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA.
³⁰ Center for Digestive Health, Section of Gastroenterology and Hepatology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
³¹ Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical System, Los Angeles, California, USA.
³² Crohn's & Colitis Foundation, New York, New York, USA.
³³ Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
³⁴ Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
³⁵ Alimentiv Inc, London, Ontario, Canada.
³⁶ Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
³⁷ Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada.
³⁸ Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.

Abstract

Introduction: Targeted immunomodulators (eg, advanced therapies) effectively achieve symptomatic remission in patients with inflammatory bowel disease (IBD). However, ~25%-50% of patients with IBD achieving symptomatic remission with an advanced therapy may have continued endoscopically/radiologically active bowel inflammation, and it is uncertain whether changing alternative advanced therapies in asymptomatic patients with IBD will reduce bowel inflammation and achieve durable deep remission.

Methods and analysis: The QUality Outcomes Treating IBD to Target (QUOTIENT) study is an open-label, multicentre, pragmatic, randomised, controlled trial that aims to compare the efficacy and safety of switching to an alternative advanced therapy targeting endoscopic/radiological remission (treat-to-target) versus continuing the initial, or index, advanced therapy, in asymptomatic patients with IBD with moderate-to-severe endoscopic/radiological bowel inflammation. Enrolment is planned for ~250 participants in Canada/USA, randomised 1:1 to switching to alternative advanced therapy or continuing index advanced therapy, and then followed 104 weeks within routine clinical practice. Patient-reported outcomes measure efficacy and quality of life/treatment burden/safety. Primary endpoint is the time from randomisation to treatment failure.

Ethics and dissemination: The study is conducted in compliance with the protocol, ICH Good Clinical Practice, applicable regulatory requirements and appropriate review boards/independent ethics committees (approval numbers: Pro00077486; Pro00061437; STUDY00002062; 22-004171; i22-01269; IRB22-0890; IRB_00154397; 2000032384; SHIRB#2022.095-2; STUDY00007146; MMC#2024-18; REB#125290; 17784; Pro00142214; 20240660-01H), with documented written informed consent. Findings will be disseminated through peer-reviewed journals, scientific presentations, and publicly available Patient-Centered Outcomes Research Institute (PCORI) websites, including lay summaries. The Crohn's & Colitis Foundation Education, Support, and Advocacy Department, and our patient advocacy stakeholder, will develop educational and marketing resources to communicate findings to a broad audience (>250 000 patients/caregivers/healthcare professionals).

Trial registration number: NCT05230173.

Keywords: CROHN'S DISEASE; IMMUNOTHERAPY; INFLAMMATORY BOWEL DISEASE.

Publication types

Clinical Trial Protocol

MeSH terms

Adult
Canada
Female
Humans
Immunomodulating Agents* / administration & dosage
Immunomodulating Agents* / therapeutic use
Inflammatory Bowel Diseases* / drug therapy
Inflammatory Bowel Diseases* / therapy
Male
Multicenter Studies as Topic
Patient Reported Outcome Measures
Pragmatic Clinical Trials as Topic
Quality of Life
Remission Induction / methods
Treatment Outcome

Substances

Immunomodulating Agents

Associated data

ClinicalTrials.gov/NCT05230173