Precision Medicine in Crohn's Disease and Ulcerative Colitis: Predicting Disease Flare and Disease progression

Crohn's disease and ulcerative colitis are the common forms of inflammatory bowel disease affecting up to 1 in 100 people in the UK. Incidence rates are increasing sharply in the previously undeveloped world, driven by urbanisation and adoption of a Western lifestyle. IBD typically manifests in adolescence / early adulthood with disturbed bowel function, a robust inflammatory response, systemic upset, psycho-social disturbance and substantial health-economic burden. Recent years have seen massive biotech / pharma investment in IBD with multiple different drug modalities now approved for use. However, remission rates are hitting a ceiling at 1 year of 30-40%, and no reliable biomarkers exist to aid with drug positioning. Management of IBD is further complicated by our inability to prognosticate on treatment response, disease flare or disease progression.

The PREdiCCt study www.predicct.co.uk, led by Dr Charlie Lees, is presently recruiting 3100 people with IBD from across the UK. Patients are recruited in clinical remission, and followed-up during two years. Detailed baseline data is collected for all patients. Among others, this includes electronic health records held by NHS, whole-genome and metabolomic sequencing, diet/lifestyle data recorded through a mobile app as well as a full blood panel. Throughout the follow-up, the mobile app is also used to regularly collect patient self-reported disease outcomes.

The overarching goal of this project is to develop and apply computational strategies which can improve the stratification and subsequent treatment of IBD patients. High-dimensional Bayesian hierarchical models will be used as a natural and powerful framework to combine information from multiple data sources, whist appropriately quantifying statistical uncertainty. In particular, we seek to address the following research questions:

1. What aspects of disease phenotype, diet, lifestyle, genetics and the gut microbiota contribute to a) disease flare, b) disease progression & c) treatment response in IBD?
2. How can we stratify patients based on disease biology and risk of progression?
3. Based on this, how can we intervene to improve patient outcomes?