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

美泊利单抗治疗严重哮喘的超极化氙 MRI：早期检测个体患者的反应

• 批准号: 10400725
• 负责人: Robert Paul Thomen
• 金额: $ 38.75万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10400725
• 关键词: Address; Affect; Asthma; Biological; Biological Markers; Biological Products; Biological Response Modifier Therapy; Bolus Infusion; Bronchodilation; Bronchodilator Agents; Chronic Obstructive Pulmonary Disease; Clinical; Clinical Management; Clinical Trials; Clinical assessments; Cystic Fibrosis; Data; Defect; Developed Countries; Development; Disease; Dose; Drug Targeting; Early Diagnosis; Etiology; Evaluation; Exhibits; Extrinsic asthma; Gases; Health Care Costs; Healthcare; Image; Imaging Techniques; Impairment; Inhalation; Interleukin-5; Lead; Leukotrienes; Lung; Magnetic Resonance Imaging; Magnetism; Maps; Measurement; Measures; Methods; Molecular; Noble Gases; Nuclear; Pathway interactions; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Physiological; Placebo Effect; Population; Process; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary function tests; Questionnaires; Refractory; Relaxation; Resolution; Savings; Severity of illness; Signal Transduction; Sputum; Steroids; Stimulus; Symptoms; Techniques; Time; Work; Xenon; airway hyperresponsiveness; airway inflammation; asthmatic; asthmatic patient; base; cohort; conventional therapy; cost; cost outcomes; efficacy evaluation; eosinophil; eosinophilic asthma; improved; improved outcome; individual patient; individual response; individualized medicine; ineffective therapies; inhibitor; mepolizumab; new therapeutic target; patient response; predicting response; primary endpoint; pulmonary function; research clinical testing; respiratory; respiratory smooth muscle; response; specific biomarkers; standard of care; treatment response; ventilation

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.

项目摘要 严重的难治性哮喘患者约占所有哮喘患者的5%，但 占所有哮喘相关医疗费用的50%以上。哮喘的生物治疗，靶向药物 特定的致病途径，特别是哮喘病例，已经开始作为第一个出现在市场上 重症哮喘的个体化治疗。目前，这些生物制剂的成本从每年10-4万美元不等。 而且并不总是能改善某些患者的哮喘症状。留住病人的临床决定 一种特定的生物学是基于12周时的加重计数和哮喘问卷回答 治疗开始后，患者已经服用了3剂(0周、4周和8周)。 加重计数和患者对问卷的回答是临床试验的主要终点。 其结果是获得批准，是用于临床反应评估的主要生物标志物，但患者- 肺功能的特定生物标志物将最有利于评估对这些患者的反应- 特定的药物。缺乏能够预测生物治疗反应的生物标志物是一个尚未满足的临床问题。 需要。这项研究将通过评估超极化129Xe磁共振成像(HPG)的潜力来解决这一未得到满足的需求 检测和预测个体患者的生物反应。超极化是一个过程，通过这个过程 129Xe的核磁性大大增强，使其可以直接通过核磁共振成像。受试者吸入 收集氙气和核磁共振成像，得到高分辨率的区域肺通气图。最重要的是 假设HPG磁共振可以在常规的临床环境中进行，并将预测哪些患者 对抗IL-5生物制剂美波利单抗的反应比标准临床提前8至12周 评估。将对计划接受美波利单抗治疗的哮喘患者进行HPG MRI检查，时间为 基线、4周和12周时间点，以评估其评估、检测和预测的潜力 患者对甲波利单抗的反应。这可能会极大地降低成本并改善这些项目的结果 病人。