TY - JOUR
T1 - 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
AU - IBD-response, CD-meta response
AU - Wyatt, Nicola J.
AU - Watson, Hannah
AU - Anderson, Carl A.
AU - Kennedy, Nicholas A.
AU - Raine, Tim
AU - Ahmad, Tariq
AU - Allerton, Dean
AU - Bardgett, Michelle
AU - Clark, Emma
AU - Clewes, Dawn
AU - Martin, Cristina Cotobal
AU - Doona, Mary
AU - Doyle, Jennifer A.
AU - Frith, Katherine
AU - Hancock, Helen C.
AU - Hart, Ailsa L.
AU - Hildreth, Victoria
AU - Irving, Peter M.
AU - Iqbal, Sameena
AU - Kennedy, Ciara
AU - King, Andrew
AU - Lawrence, Sarah
AU - Lees, Charlie W.
AU - Lees, Robert
AU - Letchford, Laura
AU - Liddle, Trevor
AU - Lindsay, James O.
AU - Maier, Rebecca H.
AU - Mansfield, John C.
AU - Marchesi, Julian R.
AU - McGregor, Naomi
AU - McIntyre, Rebecca E.
AU - Ostermayer, Jasmin
AU - Osunnuyi, Tolulope
AU - Powell, Nick
AU - Prescott, Natalie J.
AU - Satsangi, Jack
AU - Sharma, Shriya
AU - Shrestha, Tara
AU - Speight, Ally
AU - Strickland, Michelle
AU - Wason, James M.S.
AU - Whelan, Kevin
AU - Wood, Ruth
AU - Young, Gregory R.
AU - Zhang, Xinyue
AU - Parkes, Miles
AU - Stewart, Christopher J.
AU - Jostins-Dean, Luke
AU - Lamb, Christopher A.
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.
PY - 2024/4/17
Y1 - 2024/4/17
N2 - 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.ibdresponse.co.uk.
AB - 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.ibdresponse.co.uk.
UR - http://www.scopus.com/inward/record.url?scp=85190889636&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2023-073639
DO - 10.1136/bmjopen-2023-073639
M3 - Article
C2 - 38631839
AN - SCOPUS:85190889636
SN - 2044-6055
VL - 14
JO - BMJ Open
JF - BMJ Open
IS - 4
M1 - e073639
ER -