BMJ Open. 2024 Apr 17;14(4):e073639. doi: 10.1136/bmjopen-2023-073639.

Nicola J Wyatt ^1 2, Hannah Watson ¹, Carl A Anderson ³, Nicholas A Kennedy ^4 5, Tim Raine ⁶, Tariq Ahmad ^4 5, Dean Allerton ⁷, Michelle Bardgett ⁷, Emma Clark ⁷, Dawn Clewes ⁷, Cristina Cotobal Martin ³, Mary Doona ², Jennifer A Doyle ¹, Katherine Frith ⁷, Helen C Hancock ⁷, Ailsa L Hart ^8 9, Victoria Hildreth ⁷, Peter M Irving ^10 11, Sameena Iqbal ³, Ciara Kennedy ⁷, Andrew King ², Sarah Lawrence ⁷, Charlie W Lees ^12 13, Robert Lees ², Laura Letchford ³, Trevor Liddle ¹⁴, James O Lindsay ^15 16, Rebecca H Maier ⁷, John C Mansfield ^1 2, Julian R Marchesi ¹⁷, Naomi McGregor ⁷, Rebecca E McIntyre ³, Jasmin Ostermayer ³, Tolulope Osunnuyi ³, Nick Powell ^17 18, Natalie J Prescott ¹⁹, Jack Satsangi ²⁰, Shriya Sharma ⁷, Tara Shrestha ⁷, Ally Speight ^1 2, Michelle Strickland ³, James Ms Wason ²¹, Kevin Whelan ²², Ruth Wood ⁷, Gregory R Young ¹, Xinyue Zhang ²¹, Miles Parkes ⁶, Christopher J Stewart ¹, Luke Jostins-Dean ²³, Christopher A Lamb ^24 2

Author information

¹Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.

²Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

³Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.

⁴Department of Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.

⁵Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.

⁶Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

⁷Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK.

⁸Department of Gastroenterology, St Mark's Hospital and Academic Institute, London, UK.

⁹Department of Surgery and Cancer, Imperial College London, London, UK.

¹⁰Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

¹¹School of Immunology & Microbial Sciences, King's College London, London, UK.

¹²Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK.

¹³Edinburgh IBD Unit, Western General Hospital, NHS Lothian, Edinburgh, UK.

¹⁴Research Informatics Team, Clinical Research, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

¹⁵Department of Gastroenterology, Barts Health NHS Trust, London, UK.

¹⁶Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK.

¹⁷Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, St Mary's Hospital, Imperial College London, London, UK.

¹⁸Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK.

¹⁹Department of Medical and Molecular Genetics, Guy's Hospital, King's College London, London, UK.

²⁰Nuffield Department of Medicine, University of Oxford, Oxford, UK.

²¹Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.

²²Department of Nutritional Sciences, King's College London, London, UK.

²³Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.

²⁴Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK christopher.lamb@newcastle.ac.uk.

Abstract

Introduction: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments.

Methods and analysis: This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures.

Ethics and dissemination: Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk.

Trial registration number: ISRCTN96296121.