METHYLOMIC_DNA methylation markers to predict treatment success of biologicals in Crohn’s disease

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Monoclonal antibodies have become a mainstay of therapy in common immune-mediated diseases (IMID) including Crohn’s disease(CD), rheumatoid arthritis (RA), and psoriasis (PsO). Current therapeutics include antibodies (“biologicals”) targeting inflammatoryproteins such as Tumor Necrosis Factor (adalimumab), leukocyte trafficking (vedolizumab), or IL-12/IL-23 (ustekinumab). At presenthowever, it cannot be predicted which biological will be effective in an individual patient, with only <40% of patients showing primaryresponse to any given therapeutic. Treatment failure is associated with disease complications, and increased health care costs.. Hencethe overwhelming need for predictive biomarkers to guide personalised medicine in IMID is evident. No biomarker to target therapyis validated in clinical practice. In METHYLOMIC, we build on multiple previous cohort studies in which we confirmed epigeneticbiomarkers (specifically DNA methylation) as the most stringent predictor of response to biological therapy, zooming in on CD.Specifically, we discovered and validated differential DNA methylation profiles in peripheral blood as biomarkers of response/deepremission for 3 approved biologicals in CD. Through the use of machine learning algorithms, treatment response could be predicted withup to 93% accuracy for each biological for CD, and RA. METHYLOMICS is committed to bringing personalised treatment-selection inCD and other IMID to clinical practice. We have teamed up clinical, epigenetic, and DNA diagnostics experts, patient organisations, andcompanies across Europe, for further validation studies, develop a marketable rapid targeted methylation assay that we than validate in aunique prospective randomised clinical trial for CD. Efficiency and cost-effectiveness is assessed in great detail and regulatory approvalis guided by experts to assure delivery of the first epigenetic kit personalised treatment of CD.