Price David, Østrem Anders, Thomas Mike, Welte Tobias
Department of Primary Care Respiratory Medicine, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; Observational and Pragmatic Research Institute, Singapore.
Gransdalen Legesenter, Oslo, Norway.
Int J Chron Obstruct Pulmon Dis. 2016 Dec 30;12:141-168. doi: 10.2147/COPD.S116719. eCollection 2017.
Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β-agonist [LABA]) are available for the treatment of COPD. Studies of these FDCs have demonstrated substantial improvements in lung function (forced expiratory volume in 1 second) in comparison with their respective constituent monocomponents. Improvements in patient-reported outcomes (PROs), such as symptoms and health status, as well as exacerbation rates, have been reported compared with a LABA or LAMA alone, but results are less consistent. The inconsistencies may in part be owing to differences in study design, methods used to assess study end points, and patient populations. Nevertheless, these observations tend to support an association between improvements in forced expiratory volume in 1 second and improvements in symptom-based outcomes. In order to assess the effects of FDCs on PROs and evaluate relationships between PROs and changes in lung function, we performed a systematic literature search of publications reporting randomized controlled trials of FDCs. Results of this literature search were independently assessed by two reviewers, with a third reviewer resolving any conflicting results. In total, 22 Phase III randomized controlled trials of FDC bronchodilators in COPD were identified, with an additional study including a post-literature search (ten for indacaterol-glycopyrronium once daily, eight for umeclidinium-vilanterol once daily, three for tiotropium-olodaterol once daily, and two for aclidinium-formoterol twice daily). Results from these studies demonstrated that the LAMA-LABA FDCs significantly improved lung function compared with their component monotherapies or other single-agent treatments. Furthermore, LABA-LAMA combinations also generally improved symptoms and health status versus monotherapies, although some discrepancies between lung function and PROs were observed. Overall, the safety profiles of the FDCs were similar to placebo. Further research is required to examine more closely any relationship between lung function and PROs in patients receiving LABA-LAMA combinations.
几种长效支气管扩张剂（一种长效毒蕈碱拮抗剂[LAMA]加一种长效β受体激动剂[LABA]）的固定剂量复方制剂（FDC）可用于慢性阻塞性肺疾病（COPD）的治疗。对这些FDC的研究表明，与各自的单一成分相比，其肺功能（1秒用力呼气量）有显著改善。与单独使用LABA或LAMA相比，患者报告的结局（PRO），如症状和健康状况以及急性加重率有所改善，但结果不太一致。这些不一致可能部分归因于研究设计、评估研究终点的方法以及患者群体的差异。尽管如此，这些观察结果倾向于支持1秒用力呼气量的改善与基于症状的结局改善之间的关联。为了评估FDC对PRO的影响并评估PRO与肺功能变化之间的关系，我们对报告FDC随机对照试验的出版物进行了系统的文献检索。两位评审员独立评估了该文献检索的结果，第三位评审员解决任何相互矛盾的结果。总共确定了22项COPD中FDC支气管扩张剂的III期随机对照试验，另有一项研究包括文献检索后补充（每日一次茚达特罗-格隆溴铵10项，每日一次乌美溴铵-维兰特罗8项，每日一次噻托溴铵-奥达特罗3项，每日两次阿地溴铵-福莫特罗2项）。这些研究的结果表明，与各自的单一疗法或其他单药治疗相比，LAMA-LABA FDC显著改善了肺功能。此外，与单一疗法相比，LABA-LAMA联合用药通常也改善了症状和健康状况，尽管在肺功能和PRO之间观察到一些差异。总体而言，FDC的安全性与安慰剂相似。需要进一步研究，以更密切地检查接受LABA-LAMA联合用药的患者肺功能与PRO之间的任何关系。
