Identification of novel molecular drivers, prognostic and diagnostic biomarkers for inflammatory bowel disease (IBD): protocol for the Nottingham/AstraZeneca prospective IBD observational cohort study

Introduction

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, inflammatory bowel diseases (IBDs) of unknown origin, affecting the gastrointestinal tract and often causing extraintestinal symptoms. Conventional treatments (eg, glucocorticosteroids, immunomodulators) and targeted advanced treatments, including anti-TNFα, antibodies to p40 subunit of IL-12/23, antibodies to p19 subunit of IL-23, anti-α4β7 integrin, Janus kinase inhibitors (JAKis) and sphingosine-1-phosphate receptor (S1PR) modulators, do not achieve sustained responses for all patients, leaving significant unmet therapeutic needs.

Methods and analysis

This prospective, multi-centre observational study will follow a cohort of 240 patients across multiple study centres within NHS trusts in the UK who are initiating or switching biologics, specifically anti-TNFα and anti-α4β7 integrin for UC, and anti-TNFα, antibodies to p40 subunit of IL-12/2 and JAKi for CD. Through comprehensive profiling of immunological, transcriptional, microbiome, genetic and proteomic markers at baseline, week 12, and week 52, this study aims to uncover non-invasive biomarkers that predict response to these drug classes, ultimately advancing personalised medicine in IBD.

Ethics and dissemination

Ethical approval for the Nottingham/AstraZeneca study was granted by the West of Scotland Research Ethics Committee. Recruitment began in December 2022 and is currently ongoing at 10 NHS Trust sites across the UK. Study findings will be disseminated by publication in peer-reviewed journals and presentations at relevant national and international conferences.