Biomarkers of relapse in UC on maintenance Tofacitinib (BRITE)
Research type
Research Study
Full title
Biomarkers of Relapse In ulcerative colitis patients after Tofacitinib dose rEduction (BRITE)
IRAS ID
276727
Contact name
Peter Irving
Contact email
Sponsor organisation
Guy's & St Thomas' Foundation NHS Trust
Duration of Study in the UK
1 years, 11 months, 29 days
Research summary
Tofacitinib is an orally administered drug that has been shown to be effective in patients with moderate to severe ulcerative colitis (UC), an incurable, chronic inflammatory condition of the large bowel. The tofacitinib clinical trials demonstrate that the 10mg twice daily maintenance dose is superior to the 5mg twice daily dose in those with prior treatment failure for UC. Accordingly, many practitioners favour continuing the 10mg twice daily dose in higher risk patients with prior treatment resistant disease, rather than dropping to the 5mg twice daily maintenance dose at week 8 (or week 16 in those slower to respond).
This dosing decision needs to be balanced against the potential risk of continuing at the higher dose; there is a higher risk of side effects such as infection and blood clots with the 10mg twice daily dose.
Given that most patients who are receiving tofacitinib are treatment resistant, there is an urgent need to identify ways to predict which patients more likely to flare should they dose reduce. Such biomarkers would enable us to risk stratify our patients at the point of consideration of dose reduction, to enable assessment of the risk and benefit of dose reduction versus continuation at the higher dose.
This study aims to explore clinical and laboratory based markers (from blood and colon tissue), which in turn may to help make key treatment decisions for tofacitinib-treated patients. We hypothesise that patients who relapse following dose reduction will have changes in cytokine expression of their pro-inflammatory T cells in peripheral blood mononuclear cells (PBMCs), increased STAT activation in PBMCs, and possibly signature genes in their colonic tissue.
Patients will be recruited over a 12 month period from Guy's and St Thomas' NHS Foundation Trust, a large tertiary referral centre for inflammatory bowel disease.
REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
21/YH/0148
Date of REC Opinion
5 Jul 2021
REC opinion
Favourable Opinion