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

单克隆抗体已成为常见免疫介导性疾病（IMID）的主要治疗手段，包括克罗恩病（CD）、类风湿性关节炎（RA）和牛皮癣（PsO）。目前的治疗方法包括针对炎症蛋白的抗体（“生物制剂”），如肿瘤坏死因子（阿达木单抗）、白细胞运输（维多利单抗）或IL-12/IL-23 （ustekinumab）。然而，目前还无法预测哪一种生物疗法对单个患者有效，只有<40%的患者对任何一种治疗方法表现出原发性反应。治疗失败与疾病并发症和卫生保健费用增加有关。因此，对预测性生物标志物来指导IMID个性化医疗的迫切需求是显而易见的。没有生物标志物在临床实践中被证实为靶向治疗。在METHYLOMIC中，我们建立在先前的多个队列研究的基础上，在这些研究中，我们证实了表观遗传生物标志物（特别是DNA甲基化）是对生物治疗反应的最严格预测因子，放大了CD。具体来说，我们发现并验证了外周血中的差异DNA甲基化谱作为3种已批准的CD生物制剂的反应/深度预测的生物标志物。对于CD和RA，每种生物学指标的治疗反应预测准确率高达93%。METHYLOMICS致力于将个性化治疗选择inCD和其他IMID带入临床实践。我们已经与欧洲各地的临床、表观遗传学和DNA诊断专家、患者组织和公司合作，进行进一步的验证研究，开发出一种可销售的快速靶向甲基化检测方法，我们将在一项独特的前瞻性随机临床试验中对其进行验证。效率和成本效益进行了非常详细的评估，并在专家的指导下获得监管批准，以确保交付首个表观遗传学试剂盒个性化治疗CD。

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.