Mepolizumab-induced Changes in Nasal Methylome and Transcriptome to Predict Response in Asthma

We aimed to detect a predictive or early nasal gene expression and/or DNA methylation signature that could identify responders or non-responders to Mepolizumab at one year. Data for 27 asthma patients enrolled in The PROCLAIM study (Poor Response tO monoClonaL therApy In asthMa) who matched the UK NHS criteria for receiving Mepolizumab was used (ethics REC18/EM/0268). Nasal brushes were taken at baseline (pre-drug) and after 3-months of treatment. Responders were defined as patients who had a 50% reduction in oral corticoid steroid use and/or 50% reduction in exacerbation frequency after one year (NICE guidelines, TA431, 2017). Gene expression was compared between responders and non-responders at baseline and at 3 months post mepolizumab treatment.

本研究旨在挖掘可用于识别美泊利单抗（Mepolizumab）治疗一年后应答者与无应答者的预测性或早期鼻部基因表达和/或DNA甲基化特征。本研究使用了PROCLAIM研究（哮喘单克隆治疗应答不佳研究，Poor Response tO monoClonaL therApy In asthMa）中27名符合英国国家医疗服务体系（UK NHS）美泊利单抗给药标准的哮喘患者数据，伦理审批号为REC18/EM/0268。研究分别于基线（给药前）及治疗3个月后采集鼻拭子样本。本研究将应答者定义为治疗一年后口服糖皮质激素使用量降低50%和/或急性发作频率降低50%的患者，该定义遵循英国国家卫生与临床优化研究所（NICE）指南TA431（2017年）。分别在基线及美泊利单抗治疗3个月后，对比应答者与无应答者的基因表达水平。