Defining predictors of responsiveness to advanced therapies in Crohn's disease and ulcerative colitis: protocol for...

Area of Science:

• Gastroenterology and Immunology
• Microbiome Research
• Personalized Medicine

Background:

• Inflammatory bowel disease (IBD) significantly impacts quality of life due to chronic gastrointestinal inflammation.
• Current advanced therapies for IBD have high primary non-response rates (up to 40%), highlighting a critical unmet need for predictive treatment strategies.
• Existing research on the gut microbiome in IBD is limited by small sample sizes, single-treatment analyses, and heterogeneous results, hindering the development of reliable predictive signatures.

Purpose of the Study:

• To develop and validate a predictive model for patient response to advanced therapies in inflammatory bowel disease (IBD).
• To leverage multi-omic data, including microbiome, metabolome, transcriptome, and genomic information, to create a tool for personalized treatment selection in IBD.
• To ultimately improve patient quality of life, reduce risks associated with ineffective treatments, and decrease healthcare expenditure.

Main Methods:

• A prospective, multicentre, observational study involving 1325 participants commencing advanced IBD therapies across ~40 UK sites.
• Comprehensive data collection including gut microbiome, metabolome, single-cell transcriptome, human genome, dietary, and clinical data at baseline, week 14, and week 54.
• Primary outcome is clinical response at week 14, with secondary outcomes assessing remission, sustained response, corticosteroid-free outcomes, and patient-reported measures.

Main Results:

• Recruitment is ongoing, with data collection planned through week 54 for 1325 participants.
• The study will identify key multi-omic and clinical factors associated with treatment response in IBD.
• Validation of a predictive model for advanced IBD therapy response is the anticipated outcome.

Conclusions:

• The IBD-RESPONSE study is poised to deliver a novel predictive tool for personalized IBD treatment selection.
• Findings have the potential to significantly improve treatment efficacy, patient outcomes, and healthcare resource utilization in IBD management.
• The development of biomarker-based stratification and microbial target manipulation strategies are future implications of this research.