Real-world patient responsiveness & safety of long-acting beta agonists in asthma

意义重大。长效β受体激动剂(LABA)在哮喘治疗中的疗效比较 其他控制者药物尚未建立。尽管LABA单一疗法增加了严重的 不良事件(AEs)，建议与吸入性皮质类固醇(ICS)联合使用， 联合治疗的安全性尚不清楚。同样未知的，也是临床上重要的理解是如何，为什么 而LABA和/或联合治疗与严重急性脑炎风险增加相关。 明确的目标。以解决联合治疗的相对有效性和安全性问题 (ICS+LABA)，以及了解经历过AE的人的概况，以及经历过AE的人的概况 从联合治疗中获益最多，我们将(1)确定含LABA的疗效 持续性哮喘疾病管理中的治疗方法与其他现有控制方案的比较；(2) 确定含有LABA的治疗是否与哮喘相关的严重急性脑炎风险增加相关 和全因死亡率；以及(3)确定临床上对急性脑炎有反应或有急性脑血管意外的患者的特征 归因于含有LABA的疗法。 研究设计。在目标1中，我们将对患有持续性疾病的受试者进行基于总体的队列研究。 哮喘。在现实世界中，含有LABA的疗法的效果将被测量并与 1998-2010年间哮喘控制和加重预防方面的其他治疗方法。这段时间 允许在使用LABA单一疗法期间和在识别AE之前的一段时间内研究LABA 以及FDA的黑匣子警告。这项研究将在近66.4万名哮喘患者的不同人群中进行 我们已经收集了，包括州医疗补助人口，四个HMO研究人口和一个 国防部人口。在目标2中，我们将进行一项嵌套式病例对照研究，以评估 使用含LABA的疗法治疗与哮喘相关的严重急性发作。哮喘相关和全因死亡 将另行研究。在目标3中，患者特征与急性脑血管事件的反应和严重程度有关 将对含有LABA的疗法进行相关评估，包括患者人口统计、疾病严重程度、 潜在的哮喘控制、用药模式、依从性和可定义的哮喘表型 多变量回归建模。对于每个目标，各种分组分析、敏感性分析和 将进行模拟研究，以提供可靠的结果并评估估计的准确性。 冲击力。该项目至关重要，因为它解决了以下方面的相对有效性和安全问题 哮喘药物治疗。它将为医生、患者和医疗保健政策制定者提供信息并赋予其权力 提供关于如何、何时以及向谁提供或避免含有LABA的疗法的及时知识。是这样的 知识将对哮喘疾病管理产生广泛的公共卫生影响。

Significance. The comparative effectiveness of long-acting beta agonists (LABA) in asthma management with other controller medicines has not been established. Although LABA monotherapy increases the risk of serious adverse events (AEs) and is recommended to be used in combination with inhaled corticosteroids (ICS), the safety of combination therapy is not known. Also not known, and clinically important to understand, is how, why and to whom LABAs and/or combination therapy are associated with increased risk of serious AEs. Specific Aims. To address the comparative effectiveness and safety concerns of the combination therapy (ICS + LABA), as well as to understand the profile of those who experience AE, and the profile of those who benefit most from the combination therapy, we will (1) determine the effectiveness of LABA-containing therapies in comparison with other available controller regimens in persistent asthma disease management; (2) determine if LABA-containing therapies are associated with an increased risk of asthma-related serious AEs and all-cause mortality; and (3) determine the characteristics of patients who clinically respond to, or have AEs attributable to, LABA-containing therapies. Research Design. In Aim 1, we will conduct a population based cohort study of subjects with persistent asthma. The effect of LABA-containing therapies in the real-world setting will be measured and compared with other asthma controller therapies on asthma control and exacerbation prevention from 1998-2010. This period allows for the study of LABAs during use of LABA monotherapy, and during a period prior to AE recognition and the FDA black box warning. The study will be done in diverse populations of nearly 664,000 asthmatics which we have assembled, including a state Medicaid population, four HMO research populations, and a Department of Defense population. In Aim 2, we will conduct a nested case-control study to evaluate the risk of serious asthma-related AEs with the use of LABA-containing therapies. Asthma-related and all-cause death will be studied separately. In Aim 3, patient characteristics associated with both response to, and serious AEs related to, LABA-containing therapies will be assessed, including patient demographics, disease severity, underlying asthma control, medication utilization patterns, adherence, and definable asthma phenotypes using multivariable regression modeling. For each aim, various subgroup analyses, sensitivity analyses and simulation studies will be performed to provide robust results and to evaluate the accuracy of the estimates. Impact. This project is of critical importance as it addresses comparative effectiveness and safety concerns in asthma pharmacotherapy. It will inform and empower physicians, patients, and healthcare policy makers providing timely knowledge in how, when, and to whom to provide or avoid LABA containing therapies. Such knowledge will have widespread public health impact in asthma disease management.