COPD 患者每日一次单吸入器三联与双联治疗。
Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD.
机构信息
From GlaxoSmithKline, Collegeville (D.A. Lipson, J.B., S.J.P.), and the Perelman School of Medicine, University of Pennsylvania (D.A. Lipson), and Lewis Katz School of Medicine at Temple University (G.J.C.), Philadelphia - all in Pennsylvania; GlaxoSmithKline, Research Triangle Park, NC (F.B., C.E.J.); GlaxoSmithKline, Stockley Park West, Uxbridge (N.B., N.C.D., S.K., M.T.), the Department of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter (D.M.G.H.), UCL Respiratory, University College London, London (D.A. Lomas), and the Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester University NHS Foundation Trust, Manchester (D.S.) - all in the United Kingdom; the Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham (M.T.D.); the Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor (M.K.H.); the Department of Public Health, University of Copenhagen, Copenhagen (P.L.), and the Medical Department, Pulmonary Section, Herlev-Gentofte Hospital, Herlev (P.L.) - both in Denmark; New York-Presbyterian Hospital/Weill Cornell Medical Center, New York (F.J.M.); and the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (R.A.W.).
出版信息
N Engl J Med. 2018 May 3;378(18):1671-1680. doi: 10.1056/NEJMoa1713901. Epub 2018 Apr 18.
BACKGROUND
The benefits of triple therapy for chronic obstructive pulmonary disease (COPD) with an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β-agonist (LABA), as compared with dual therapy (either inhaled glucocorticoid-LABA or LAMA-LABA), are uncertain.
METHODS
In this randomized trial involving 10,355 patients with COPD, we compared 52 weeks of a once-daily combination of fluticasone furoate (an inhaled glucocorticoid) at a dose of 100 μg, umeclidinium (a LAMA) at a dose of 62.5 μg, and vilanterol (a LABA) at a dose of 25 μg (triple therapy) with fluticasone furoate-vilanterol (at doses of 100 μg and 25 μg, respectively) and umeclidinium-vilanterol (at doses of 62.5 μg and 25 μg, respectively). Each regimen was administered in a single Ellipta inhaler. The primary outcome was the annual rate of moderate or severe COPD exacerbations during treatment.
RESULTS
The rate of moderate or severe exacerbations in the triple-therapy group was 0.91 per year, as compared with 1.07 per year in the fluticasone furoate-vilanterol group (rate ratio with triple therapy, 0.85; 95% confidence interval [CI], 0.80 to 0.90; 15% difference; P<0.001) and 1.21 per year in the umeclidinium-vilanterol group (rate ratio with triple therapy, 0.75; 95% CI, 0.70 to 0.81; 25% difference; P<0.001). The annual rate of severe exacerbations resulting in hospitalization in the triple-therapy group was 0.13, as compared with 0.19 in the umeclidinium-vilanterol group (rate ratio, 0.66; 95% CI, 0.56 to 0.78; 34% difference; P<0.001). There was a higher incidence of pneumonia in the inhaled-glucocorticoid groups than in the umeclidinium-vilanterol group, and the risk of clinician-diagnosed pneumonia was significantly higher with triple therapy than with umeclidinium-vilanterol, as assessed in a time-to-first-event analysis (hazard ratio, 1.53; 95% CI, 1.22 to 1.92; P<0.001).
CONCLUSIONS
Triple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate-vilanterol or umeclidinium-vilanterol in this population. Triple therapy also resulted in a lower rate of hospitalization due to COPD than umeclidinium-vilanterol. (Funded by GlaxoSmithKline; IMPACT ClinicalTrials.gov number, NCT02164513 .).
背景
与双治疗（吸入性糖皮质激素-长效 β-激动剂或长效毒蕈碱拮抗剂-长效 β-激动剂）相比，慢性阻塞性肺疾病（COPD）患者使用吸入性糖皮质激素、长效毒蕈碱拮抗剂（LAMA）和长效 β-激动剂（LABA）三联疗法的益处尚不确定。
方法
在这项涉及 10355 例 COPD 患者的随机试验中，我们比较了每日一次的氟替卡松糠酸酯（吸入性糖皮质激素）100μg、乌美溴铵（LAMA）62.5μg 和维兰特罗（LABA）25μg 的联合治疗（三联治疗）与氟替卡松糠酸酯-维兰特罗（剂量分别为 100μg 和 25μg）和乌美溴铵-维兰特罗（剂量分别为 62.5μg 和 25μg）的疗效。每个方案均在单个 Ellipta 吸入器中给药。主要结局是治疗期间中重度 COPD 加重的年发生率。
结果
三联治疗组中中重度加重的发生率为每年 0.91 次，而氟替卡松糠酸酯-维兰特罗组为每年 1.07 次（三联治疗的比率为 0.85；95%置信区间 [CI]，0.80 至 0.90；15%差异；P<0.001），乌美溴铵-维兰特罗组为每年 1.21 次（比率为 0.75；95%CI，0.70 至 0.81；25%差异；P<0.001）。三联治疗组因严重加重而导致住院的年发生率为 0.13%，而乌美溴铵-维兰特罗组为 0.19%（比值比为 0.66；95%CI，0.56 至 0.78；34%差异；P<0.001）。吸入性糖皮质激素组肺炎发生率高于乌美溴铵-维兰特罗组，三联治疗组临床诊断肺炎的风险明显高于乌美溴铵-维兰特罗组，这是在首次事件时间分析中评估的（风险比，1.53；95%CI，1.22 至 1.92；P<0.001）。
结论
与氟替卡松糠酸酯-维兰特罗或乌美溴铵-维兰特罗相比，氟替卡松糠酸酯、乌美溴铵和维兰特罗三联疗法可降低人群中中重度 COPD 加重的发生率。三联疗法也降低了因 COPD 而住院的发生率，低于乌美溴铵-维兰特罗。（由葛兰素史克公司资助；IMPACT 临床试验.gov 编号，NCT02164513）。
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