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.

项目总结