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

意义长效β受体激动剂（LABA）在哮喘治疗中的疗效比较， 其他管制药品尚未确定。尽管LABA单药治疗会增加严重 不良事件（AE），并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。同样不为人知的是，在临床上重要的是要理解， 以及LABA和/或联合治疗与严重AE风险增加相关的患者。 具体目标。解决联合治疗的比较有效性和安全性问题 (ICS+ LABA），以及了解发生AE的患者的特征，以及 从联合治疗中获益最多，我们将（1）确定含LABA的 在持续性哮喘疾病管理中与其他可用的控制方案相比的治疗;（2） 确定含LABA的治疗是否与哮喘相关严重AE的风险增加相关 和全因死亡率;以及（3）确定临床上对AE有反应或发生AE的患者的特征 可归因于含LABA的治疗。 研究设计。在目标1中，我们将对持续性高血压受试者进行一项基于人群的队列研究。 哮喘将测量含LABA治疗在真实环境中的效果，并与 1998年至2010年期间用于哮喘控制和预防急性发作的其他哮喘控制剂治疗。此期间 允许在LABA单药治疗期间和AE识别前的一段时间内研究LABA 以及FDA的黑盒警告这项研究将在近664，000名哮喘患者的不同人群中进行 包括一个州医疗补助人群，四个HMO研究人群，和一个 国防部人口。在目标2中，我们将进行巢式病例对照研究，以评估 使用含LABA治疗的严重哮喘相关AE。哮喘相关和全因死亡 将单独研究。在目标3中，与严重AE的缓解相关的患者特征 将评估与含LABA治疗相关的风险，包括患者人口统计学资料、疾病严重程度， 基础哮喘控制、药物利用模式、依从性和使用 多元回归建模对于每个目标，进行了各种亚组分析、敏感性分析和 将进行模拟研究，以提供可靠的结果，并评估估计数的准确性。 冲击该项目至关重要，因为它解决了以下方面的比较有效性和安全性问题： 哮喘药物治疗它将告知并授权医生，患者和医疗保健政策制定者 及时了解如何、何时以及向谁提供或避免含LABA的治疗。等 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.