与吸入性糖皮质激素/长效β2受体激动剂（ICS/LABA）、长效抗胆碱能药物（LAMA）或长效β2受体激动剂/长效抗胆碱能药物（LABA/LAMA）相比，超精细三联疗法可延缓慢性阻塞性肺疾病（COPD）的临床重要恶化。
Extrafine triple therapy delays COPD clinically important deterioration vs ICS/LABA, LAMA, or LABA/LAMA.
作者信息
Singh Dave, Fabbri Leonardo M, Vezzoli Stefano, Petruzzelli Stefano, Papi Alberto
机构信息
Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK,
Section of Cardiorespiratory and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
出版信息
Int J Chron Obstruct Pulmon Dis. 2019 Feb 28;14:531-546. doi: 10.2147/COPD.S196383. eCollection 2019.
BACKGROUND
Current pharmacological therapies for COPD improve quality of life and symptoms and reduce exacerbations. Given the progressive nature of COPD, it is arguably more important to understand whether the available therapies are able to delay clinical deterioration; the concept of "clinically important deterioration" (CID) has therefore been developed. We evaluated the efficacy of the single-inhaler triple combination beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G), using data from three large 1-year studies.
METHODS
The studies compared BDP/FF/G to BDP/FF (TRILOGY), tiotropium (TRINITY), and indacaterol/glycopyrronium (IND/GLY; TRIBUTE). All studies recruited patients with symptomatic COPD, FEV <50%, and an exacerbation history. We measured the time to first CID and to sustained CID, an endpoint combining FEV, St George's Respiratory Questionnaire (SGRQ), moderate-to-severe exacerbations, and death. The time to first CID was based on the first occurrence of any of the following: a decrease of ≥100 mL from baseline in FEV, an increase of ≥4 units from baseline in SGRQ total score, the occurrence of a moderate/severe COPD exacerbation, or death. The time to sustained CID was defined as: a CID in FEV and/or SGRQ total score maintained at all subsequent visits, an exacerbation, or death.
RESULTS
Extrafine BDP/FF/G significantly extended the time to first CID vs BDP/FF (HR 0.61, <0.001), tiotropium (0.72, <0.001), and IND/GLY (0.82, <0.001), and significantly extended the time to sustained CID vs BDP/FF (HR 0.64, <0.001) and tiotropium (0.80, <0.001), with a numerical extension vs IND/GLY.
CONCLUSION
In patients with symptomatic COPD, FEV <50%, and an exacerbation history, extrafine BDP/FF/G delayed disease deterioration compared with BDP/FF, tiotropium, and IND/GLY.
TRIAL REGISTRATION
The studies are registered in ClinicalTrials.gov: TRILOGY, NCT01917331; TRINITY, NCT01911364; TRIBUTE, NCT02579850.
背景
慢性阻塞性肺疾病（COPD）的现有药物治疗可改善生活质量和症状，并减少急性加重。鉴于COPD的进展性，了解现有治疗方法是否能够延缓临床恶化可能更为重要；因此，“具有临床意义的恶化”（CID）这一概念应运而生。我们利用三项为期1年的大型研究数据，评估了丙酸倍氯米松、富马酸福莫特罗和格隆溴铵单一吸入器三联组合（BDP/FF/G）的疗效。
方法
这些研究将BDP/FF/G与BDP/FF（TRILOGY研究）、噻托溴铵（TRINITY研究）以及茚达特罗/格隆溴铵（IND/GLY；TRIBUTE研究）进行了比较。所有研究均招募了有症状的COPD患者，其第1秒用力呼气容积（FEV）<50%且有急性加重病史。我们测量了首次发生CID的时间以及持续发生CID的时间，持续发生CID这一终点指标综合了FEV、圣乔治呼吸问卷（SGRQ）、中重度急性加重和死亡情况。首次发生CID的时间基于以下任何一种情况的首次出现：FEV较基线下降≥100 mL、SGRQ总分较基线增加≥4分、发生中度/重度COPD急性加重或死亡。持续发生CID的时间定义为：在所有后续访视中FEV和/或SGRQ总分持续出现CID、发生急性加重或死亡。
结果
超细BDP/FF/G与BDP/FF相比（风险比[HR]为0.61，P<0.001）、与噻托溴铵相比（HR为0.72，P<0.001）以及与IND/GLY相比（HR为0.82，P<0.001），显著延长了首次发生CID的时间；与BDP/FF相比（HR为0.64，P<0.001）以及与噻托溴铵相比（HR为0.80，P<0.001），显著延长了持续发生CID的时间，与IND/GLY相比有数值上的延长。
结论
在有症状、FEV<50%且有急性加重病史的COPD患者中，超细BDP/FF/G与BDP/FF、噻托溴铵和IND/GLY相比，延缓了疾病恶化。
试验注册
这些研究已在ClinicalTrials.gov注册：TRILOGY研究，NCT01917331；TRINITY研究，NCT01911364；TRIBUTE研究，NCT02579850。
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