BMJ Open (Apr 2024)
Defining predictors of responsiveness to advanced therapies in Crohn’s disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine
- Peter M Irving,
- Miles Parkes,
- Ruth Wood,
- Ailsa L Hart,
- Nicholas A Kennedy,
- Nick Powell,
- Julian R Marchesi,
- Tariq Ahmad,
- Tim Raine,
- Andrew King,
- James O Lindsay,
- Kevin Whelan,
- Charlie W Lees,
- Christopher A Lamb,
- Jack Satsangi,
- Emma Clark,
- Shriya Sharma,
- Xinyue Zhang,
- Christopher J Stewart,
- Naomi McGregor,
- Helen C Hancock,
- Rebecca H Maier,
- John C Mansfield,
- Mary Doona,
- Michelle Bardgett,
- Natalie J Prescott,
- Trevor Liddle,
- Robert Lees,
- Hannah Watson,
- Carl A Anderson,
- Ally Speight,
- Ciara Kennedy,
- Sarah Lawrence,
- Nicola J Wyatt,
- Jennifer A Doyle,
- Rebecca E McIntyre,
- Luke Jostins-Dean,
- Victoria Hildreth,
- James MS Wason,
- Dean Allerton,
- Dawn Clewes,
- Cristina Cotobal Martin,
- Katherine Frith,
- Sameena Iqbal,
- Laura Letchford,
- Jasmin Ostermayer,
- Tolulope Osunnuyi,
- Tara Shrestha,
- Michelle Strickland,
- Gregory R Young
Affiliations
- Peter M Irving
- 11 School of Immunology & Microbial Sciences, King`s College London, London, UK
- Miles Parkes
- 6 Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Ruth Wood
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- Ailsa L Hart
- 8 Department of Gastroenterology, St Mark`s Hospital and Academic Institute, London, UK
- Nicholas A Kennedy
- 4 Department of Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
- Nick Powell
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
- Julian R Marchesi
- 17 Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, St Mary’s Hospital, Imperial College London, London, UK
- Tariq Ahmad
- 4 Department of Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
- Tim Raine
- 6 Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Andrew King
- 2 Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- James O Lindsay
- 16 Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK
- Kevin Whelan
- 22 Department of Nutritional Sciences, King`s College London, London, UK
- Charlie W Lees
- 12 Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK
- Christopher A Lamb
- 1 Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Jack Satsangi
- 20 Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Emma Clark
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- Shriya Sharma
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- Xinyue Zhang
- 21 Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Christopher J Stewart
- 1 Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Naomi McGregor
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- Helen C Hancock
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- Rebecca H Maier
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- John C Mansfield
- 2 Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Mary Doona
- 2 Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Michelle Bardgett
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- Natalie J Prescott
- 19 Department of Medical and Molecular Genetics, Guy`s Hospital, King`s College London, London, UK
- Trevor Liddle
- 14 Research Informatics Team, Clinical Research, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Robert Lees
- 2 Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Hannah Watson
- 1 Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Carl A Anderson
- 3 Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
- Ally Speight
- 1 Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Ciara Kennedy
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- Sarah Lawrence
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- Nicola J Wyatt
- 1 Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Jennifer A Doyle
- 1 Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Rebecca E McIntyre
- 3 Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
- Luke Jostins-Dean
- 23 Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
- Victoria Hildreth
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- James MS Wason
- 21 Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Dean Allerton
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- Dawn Clewes
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- Cristina Cotobal Martin
- 3 Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
- Katherine Frith
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- Sameena Iqbal
- 3 Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
- Laura Letchford
- 3 Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
- Jasmin Ostermayer
- 3 Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
- Tolulope Osunnuyi
- 3 Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
- Tara Shrestha
- 7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
- Michelle Strickland
- 3 Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
- Gregory R Young
- 1 Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- DOI
- https://doi.org/10.1136/bmjopen-2023-073639
- Journal volume & issue
-
Vol. 14,
no. 4
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.