Hyperpolarized xenon MRI in treatment of severe asthma by mepolizumab: toward earlier detection of individual patient responses

项目摘要 重度难治性哮喘患者约占所有哮喘患者的5%，但与哮喘的发病有关。 占所有哮喘相关医疗费用的50%以上。哮喘的生物治疗药物， 特别是哮喘病例的特定病因学途径，已经开始在市场上出现， 严重哮喘的个体化治疗。这些生物制剂的成本目前在每年10 - 40 k美元之间 并且并不总是改善某些患者的哮喘症状。临床决定让病人继续 一种特定的生物制剂是基于12周时的急性发作计数和哮喘问卷回答。 治疗开始后，此时患者已接受3次给药（第0周、第4周和第8周）。 急性加重计数和患者对问卷的应答是临床试验的主要终点 这导致了批准，并且是用于临床缓解评价的主要生物标志物，但患者- 肺功能特异性生物标志物对于评价对这些患者的反应是最有益的， 具体药物。缺乏可以预测对生物治疗的反应的生物标志物是一个未满足的临床需求。 需要的本研究将通过评价超极化129 MRI（HPG）的潜力来解决这一未满足的需求 检测和预测个体患者的生物学反应。超极化是一个过程， 129 Ω的核磁被大大增强，使其能够通过MRI直接成像。受试者吸入 氙气和MRI被收集，产生局部肺通气的高分辨率图。总体 假设HPG MR可以在常规临床环境中进行，并将预测哪些患者 对美泊利单抗（一种抗IL-5生物制剂）治疗的反应比标准临床试验早8至12周。 考核HPG MRI将在计划接受美泊利珠单抗治疗的哮喘患者中进行， 基线、4周和12周时间点，以评估其评估、检测和预测 患者对美泊利单抗的反应。这可能会大大降低成本，并改善这些结果 患者

Project Summary Patients with severe, refractory asthma constitute approximately 5% of all asthma patients but are responsible for over 50% of all asthma-related healthcare costs. Biologic treatments for asthma, drugs which target specific etiological pathways in particular asthma cases, have begun to emerge in the market as the first individualized treatments for severe asthma. Cost of these biologics currently ranges from $10-$40k per year and does not always improve asthma symptoms in some patients. The clinical decision to keep a patient on a particular biologic is based on exacerbation count and asthma questionnaire responses at 12 weeks following treatment initiation, by which time the patient has had 3 doses (at 0 weeks, 4 weeks, and 8 weeks). Exacerbation count and patient responses to questionnaires were the primary endpoints of the clinical trials which resulted in approval and are the primary biomarkers used in clinical evaluation of response, but patient- specific biomarkers of lung function would be most beneficial for evaluation of response to these patient- specific drugs. The lack of biomarkers which can predict response to biologic treatment is an unmet clinical need. This study will address this unmet need by evaluating the potential of hyperpolarized 129Xe MRI (HPG) to detect and predict biologic response in individual patients. Hyperpolarization is the process by which the nuclear magnetism of 129Xe is greatly enhanced allowing it to be directly imaged by MRI. Subjects inhale the xenon gas, and MRI are collected yielding high-resolution maps of regional lung ventilation. The overarching hypothesis is that HPG MR can be performed in a routine clinical setting and will predict which patients respond to treatment with mepolizumab, an anti-IL-5 biologic, 8 to 12 weeks sooner than standard clinical assessment. HPG MRI will be performed in asthma patients slated to receive treatment by mepolizumab at baseline, 4-week, and 12-week time points in order to assess its potential to assess, detect, and predict patient response to mepolizumab. This may dramatically reduce costs and improve outcomes for these patients.