Epigenetic predictors of biologic therapy response in Crohn's disease
Research type
Research Study
Full title
Development and validation of an epigenetic biomarker that predicts treatment success and allows personalised management in Crohn’s disease: EPIC-CD
IRAS ID
266041
Contact name
Jack Satsangi
Contact email
Sponsor organisation
University of Oxford
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Research Summary: The chronic inflammatory bowel diseases (IBD); Crohn’s disease (CD) and ulcerative colitis (UC) are common causes of chronic ill heath in Europe and North America, with an estimated disease prevalence of 0.5-1.0% overall.
The use of biologics, such as anti-TNF, has revolutionised the care of patients with CD. Nevertheless, up to 70% of patients do not respond to such biologic treatment or lose response over time. This outcome is consistent across all biological medication currently available such as the anti-TNFs infliximab (IFX) and adalimumab (ADA), the anti-integrin vedolizumab (VEDO), and the anti-p40 antibody ustekinumab (USTE).
Current treatment algorithms are largely based on a trial-and-error approach as no biologic parameters have been identified that predict treatment success or failure. As such, many patients receive ineffective treatment for many months to years, with associated complications.
The contribution of epigenetic alterations (mechanisms that switch genes on or off) in IBD is an emerging concept with work showing that specific epigenetic marks characterise patients with CD. Recently, we discovered specific epigenetic patterns in the peripheral blood prior to starting treatment that were associated with treatment response to several biologic agents in CD.
The key question we are trying to address is how to predict response to biologic treatment. Our ultimate aim would be to create a test that can predict which patient would respond best to which drug. Whilst the epigenetic alterations in IBD hold promise, we hypothesise that combining this information with analysis of the microbiome (the bacteria living in the gut) will improve the accuracy of the predictive test.
To answer these questions, we propose to collect blood tests and a rectal (gut) biopsy endoscopically prior to starting a biologic agent across participating sites. The patients will then be followed up to assess response to treatment with bloods and a further endoscopy.
Summary of results: There are no study results available for this study. The study was put through REC and set up as a study in order to set up sites other than Oxford within the Thames Valley to help with recruitment, (Oxford was recruiting under the Oxford Biobank ethics (Oxford Gastrointestinal (GI) Cohort, REC Ref 21/YH/0206, IRAS Ref 301652), principally because as one of four arms of this observational study (specifically predicting clinical response to infliximab use) was proving more challenging to reach the recruitment target. However, in the period after the pandemic, sufficient resources were not available to take this forward in Thames Valley. Following discussion with the team in Amsterdam, alternative arrangements were made in Amsterdam to recruit into this arm of the study; and the study was closed in Oxford and Thames Valley.
REC name
London - Westminster Research Ethics Committee
REC reference
21/PR/0010
Date of REC Opinion
24 Mar 2021
REC opinion
Further Information Favourable Opinion