Despite the fact that Crohn’s disease isn’t incredibly rare, existing treatments have several shortcomings. Crohn’s disease is complex because the cause is unknown, and many genetic and environmental factors contribute to colon inflammation.
Current biological therapies include TNF infliximab and adalimumab. The response rates to these treatments are highly variable (approximately 25–70%), and many patients undergo ineffective treatments for months, increasing risk and reducing quality of life. Therefore, there is a demand to predict which patients will respond to which therapies before starting treatment.
Wouter De Jonge, Professor of Neurogastroenterology, Amsterdam UMC and his team are currently conducting a trial to guide up to 380 newly diagnosed Crohn’s disease patients using a methylome-based assay to improve treatment effectiveness. The crux of his research looks at using DNA methylation patterns from the peripheral blood to predict patient response to three biological treatments (adalimumab, vedolizumab, Ustekinumab). De Jonge added that a key application of DNA methylation as an epigenetic marker is its high stability and its can also be measure using EPIC arrays.
The preliminary studies used peripheral blood DNA from patients staring adalimumab, assessing methylation patterns before and after 8 weeks of therapy. Later the study expanded to include patients on adalimumab, vedolizumab and Ustekinumab using machine learning to identify predictive methylation markers. De Jonge noted that some methylation markers were even able to distinguish responders from non-responders before treatment had even begun.
The ongoing OMICHROHN trial involves nearly 400 Crohn's patients across seven EU countries, comparing standard care to precision care guided by the methylome assay. The goal of the project is to improve endoscopic response rates by at least 15% over routine care. Furthermore, the team is developing a rapid, flexible assay platform aiming for a two-week turnaround from blood sample to result.
In summary, this research represents a major contribution toward developing personalised therapies for Crohn’s disease, thus reducing ineffective treatments and improving patient outcomes.
