Vincent W Joustra, Andrew Yung Fong Li Yim, Peter Henneman, Ishtu L Hageman, Tristan de Waard, Evgeni Levin, Alexandra Noble, Thomas P Chapman, Femke Mol, Sarah van Zon, Donghyeok Lee, Colleen GC McGregor, Alex T Adams, Jack J Satsangi, Wouter J de Jonge, Geert R D'Haens, EPIC-CD Consortium
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引用次数: 0
摘要
目前，生物疗法已广泛应用于克罗恩病（CD）的治疗，随机试验和实际经验都证明了其疗效。原发性无应答是一个常见的问题，却鲜为人知。我们评估了血液甲基化作为对维妥珠单抗（VDZ，抗a4b7整合素）或乌斯特库单抗（USTE，抗IL-12/23p40）反应的预测因素。我们报告了一项双中心前瞻性队列研究，在发现队列（n=126）和外部验证队列（n=58）中，我们分析了184名成年男性和女性CD患者在接受VDZ或USTE治疗前和治疗期间的外周血DNA甲基组。我们定义了表观遗传生物标志物，这些标志物随时间变化稳定，并与 VDZ 或 USTE 的临床和内镜综合反应相关，其曲线下面积 (AUC) 分别为 0.87 和 0.89。我们在外部队列中验证了这些模型，结果显示 VDZ 和 USTE 的曲线下面积均为 0.75。现在，我们将在一项多中心随机临床试验中对这些数据进行前瞻性测试。
Peripheral blood DNA methylation signatures predict response to vedolizumab and ustekinumab in adult patients with Crohn's disease: The EPIC-CD study
Biological therapeutics are now widely used in Crohn′s disease (CD), with evidence of efficacy from randomized trials and real-world experience. Primary non-response is a common, poorly understood problem. We assessed blood methylation as a predictor of response to vedolizumab (VDZ, anti-a4b7 integrin) or ustekinumab (USTE, anti-IL-12/23p40). We report a two-center, prospective cohort study in which we profiled the peripheral blood DNA methylome of 184 adult male and female CD patients prior to and during treatment with VDZ or USTE in a discovery (n=126) and an external validation cohort (n=58). We defined epigenetic biomarkers that were stable over time and associated with combined clinical and endoscopic response to VDZ or USTE with an area under curve (AUC) of 0.87 and 0.89, respectively. We validated these models in an external cohort yielding an AUC of 0.75 for both VDZ and USTE. These data will now be prospectively tested in a multicenter randomized clinical trial.
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