ECCO Grant Study Synopsis: Neil Chanchlani
Neil Chanchlani, ECCO Grant Awardee
Understanding the mechanisms of anti-TNF treatment failure in patients with Crohn’s Disease: a proteomic analysis of the PANTS cohort
© Neil Chanchlani
Aim of research
In the Personalised Anti-TNF Therapy in Crohn’s Disease (PANTS) prospective cohort study, we followed 1,610 patients with Crohn’s Disease treated with infliximab or adalimumab for three years. About one in four patients experienced primary non-response and one-third of initial responders lost response, leaving only one-third in remission at one year.
A limited number of proteomic markers have been implicated in anti-TNF treatment failure, but their relative effects and interactions have not been fully explored. We aim:
- To identify novel protein biomarkers linked to intestinal inflammation and immunity that influence pharmacokinetic or pharmacodynamic related primary non-response and non-remission at one year, using two multiplex Olink proteomic panels.
- Validate previously postulated protein markers associated with anti-TNF primary non-response and non-remission at one year, including TREM-1, oncostatin M, Vitamin D, ASCA, ANCA and anti-OmpC.
Methodology/experiments that will be used
This study forms part of a comprehensive multi-omic profiling project using biobanked samples from the PANTS study. We will use high-throughput immunoassays to study the serum proteome to further understand the mechanisms of anti-TNF treatment failure. We will undertake multivariable logistic regression analyses to identify factors independently associated with primary non-response and non-remission.
Anticipated main impact
We hope this study will benefit patients with Crohn’s Disease by identifying those most at risk of anti-TNF treatment failure before treatment is started and/or at the end of induction therapy. Patients at risk of anti-TNF treatment failure might be offered alternative medications or monitoring may be intensified. We hope healthcare providers will benefit from increased stratification of therapy, saving costly investigations and hospitalisation.
Testing candidate biomarkers using the Olink platforms will be done in parallel with validation of previously postulated biomarkers over three months. Analysis of the data and replication of findings in independent cohorts will be done in the subsequent six months.