PROBIT
Research type
Research Study
Full title
PREDICTORS OF RESPONSE TO BIOLOGICAL THERAPY IN ULCERATIVE COLITIS
IRAS ID
209167
Contact name
Sreedhar Subramanian
Contact email
Sponsor organisation
Royal Liverpool University Hospital
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
We propose to identify novel predictors of response to therapy in ulcerative colitis (UC) to biological drugs. The medical treatment of UC has recently been enhanced by the addition of biologics which target specific molecules. Currently, there are two classes of biological drugs: anti-tumour necrosis factor (TNF) agents such as infliximab, adaalimumab or golimumab which target the inflammatory molecule TNF and anti-adhesion drugs such as vedolizumab which block the migration of inflammatory cells to the gut. Response to biological drugs is variable with response rates of 64.5%, 50.4%, 51.0%, 47.1% for infliximab, adalimumab, golimumab and vedolizumab, respectively. There are no clear indicators of which patient is likely to respond to one or the other class of biological agent making the choice arbitrary. Identifying accurate predictors has several advantages including avoidance of adverse reactions from unnecessary exposure to treatment, minimising time spent with active disease and, finally, cost-savings. So far, gene expression at the level of the bowel lining (mucosa) appears to have the best predictive ability to identify responders to anti-TNF agents. However, such studies have not been done for the recently introduced anti-adhesion drug, vedolizumab. Moreover, mucosal gene studies involve an invasive endoscopic examination of the bowel. A recent landmark study was able to identify the presence of two distinct prognostic groups in inflammatory bowel disease by looking at gene expression from peripheral blood immune cells. The two groups were otherwise clinically indistinguishable. This strategy has not been utilised to identify responders to biological drugs in UC. In this pilot study, using gene expression in peripheral blood, our aim is to identify novel predictors of response to therapy in UC to biological drugs that will improve the use of these expensive drugs to benefit patients. Biopsies will be collected as part of the study protocol for later analysis.
REC name
North West - Liverpool Central Research Ethics Committee
REC reference
16/NW/0626
Date of REC Opinion
21 Oct 2016
REC opinion
Further Information Favourable Opinion