Development and validation of peripheral blood DNA methylation signatures to predict response to biological therapy in adults with Crohn's disease (EPIC-CD): an epigenome-wide association study
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View abstract on PubMed
Summary
This summary is machine-generated.DNA methylation can predict treatment response in Crohn's disease patients, particularly for vedolizumab and ustekinumab. This personalized medicine approach shows promise, outperforming current clinical decision support tools.
Area Of Science
- Genomics and epigenetics
- Gastroenterology
- Immunology
Background
- Crohn's disease (CD) treatment relies on biological therapies with variable efficacy.
- Primary non-response to these treatments is a significant clinical challenge.
- Predicting treatment response is crucial for personalized medicine in CD.
Purpose Of The Study
- To investigate DNA methylation patterns as predictors of treatment response to adalimumab, vedolizumab, and ustekinumab in Crohn's disease.
- To compare the predictive accuracy of DNA methylation models with existing clinical decision support tools (CDSTs).
Main Methods
- An epigenome-wide association study (EWAS) utilizing discovery (Amsterdam) and validation (Oxford) biobanks.
- Inclusion of adult patients with active Crohn's disease scheduled for biologic therapy (adalimumab, vedolizumab, ustekinumab).
- Machine learning (stability selected gradient boosting) applied to baseline DNA methylation data to predict treatment response, defined by combined endoscopic and clinical/biochemical criteria.
Main Results
- A panel of DNA methylation biomarkers was identified, showing predictive value for vedolizumab (AUC 0.75) and ustekinumab (AUC 0.75) in the validation cohort.
- The methylation models outperformed CDSTs for vedolizumab (AUC 0.56) and ustekinumab (AUC 0.66) in the validation cohort.
- Predictive accuracy was reduced in patients with prior anti-TNF exposure and not observed for adalimumab response.
Conclusions
- DNA methylation serves as a potential biomarker for predicting response to vedolizumab and ustekinumab in Crohn's disease.
- These methylation-based models offer a personalized medicine approach, outperforming current CDSTs in biologically naive patients.
- Further validation in a multicenter randomized clinical trial is ongoing for vedolizumab and ustekinumab prediction models.
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