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
{"title":"Peripheral blood DNA methylation signatures predict response to vedolizumab and ustekinumab in adult patients with Crohn's disease: The EPIC-CD study","authors":"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","doi":"10.1101/2024.07.25.24310949","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"45 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"medRxiv - Gastroenterology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.07.25.24310949","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
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.