1 GlaxoSmithKline, King of Prussia, Pennsylvania.
2 Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Am J Respir Crit Care Med. 2017 Aug 15;196(4):438-446. doi: 10.1164/rccm.201703-0449OC.
Randomized data comparing triple therapy with dual inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) are limited.
We compared the effects of once-daily triple therapy on lung function and health-related quality of life with twice-daily ICS/LABA therapy in patients with COPD.
The FULFIL (Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy) trial was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticasone furoate/umeclidinium/vilanterol 100 μg/62.5 μg/25 μg; ELLIPTA inhaler) with twice-daily ICS/LABA therapy (budesonide/formoterol 400 μg/12 μg; Turbuhaler). A patient subgroup remained on blinded treatment for up to 52 weeks. Co-primary endpoints were change from baseline in trough FEV and in St. George's Respiratory Questionnaire (SGRQ) total score at Week 24.
In the intent-to-treat population (n = 1,810) at Week 24 for triple therapy (n = 911) and ICS/LABA therapy (n = 899), mean changes from baseline in FEV were 142 ml (95% confidence interval [CI], 126 to 158) and -29 ml (95% CI, -46 to -13), respectively, and mean changes from baseline in SGRQ scores were -6.6 units (95% CI, -7.4 to -5.7) and -4.3 units (95% CI, -5.2 to -3.4), respectively. For both endpoints, the between-group differences were statistically significant (P < 0.001). There was a statistically significant reduction in moderate/severe exacerbation rate with triple therapy versus dual ICS/LABA therapy (35% reduction; 95% CI, 14-51; P = 0.002). The safety profile of triple therapy reflected the known profiles of the components.
These results support the benefits of single-inhaler triple therapy compared with ICS/LABA therapy in patients with advanced COPD. Clinical trial registered with www.clinicaltrials.gov (NCT02345161).
比较慢性阻塞性肺疾病（COPD）患者三联吸入治疗与双吸入糖皮质激素（ICS）/长效β-激动剂（LABA）治疗的随机数据有限。
我们比较了每日一次三联治疗对 COPD 患者肺功能和健康相关生活质量的影响与每日两次 ICS/LABA 治疗的影响。
FULFIL（慢性阻塞性肺疾病中闭合三联治疗的肺功能和生活质量评估）试验是一项随机、双盲、双模拟研究，比较了每日一次三联治疗（糠酸氟替卡松/乌美溴铵/维兰特罗 100μg/62.5μg/25μg；ELLIPTA 吸入器）与每日两次 ICS/LABA 治疗（布地奈德/福莫特罗 400μg/12μg；Turbuhaler）的疗效。患者亚组在 52 周内继续接受盲法治疗。主要共同终点是第 24 周时谷值 FEV1 和圣乔治呼吸问卷（SGRQ）总分的自基线变化。
在意向治疗人群（n=1810）中，三联治疗组（n=911）和 ICS/LABA 治疗组（n=899）在第 24 周时，FEV1 的自基线平均变化分别为 142ml（95%置信区间[CI]，126 至 158）和-29ml（95%CI，-46 至-13），SGRQ 评分的自基线平均变化分别为-6.6 单位（95%CI，-7.4 至-5.7）和-4.3 单位（95%CI，-5.2 至-3.4）。两个终点的组间差异均具有统计学意义（P<0.001）。与双 ICS/LABA 治疗相比，三联治疗组的中重度恶化率显著降低（降低 35%；95%CI，14%至 51%；P=0.002）。三联治疗的安全性特征反映了其各组成部分的已知特征。
这些结果支持在晚期 COPD 患者中，与 ICS/LABA 治疗相比，单吸入器三联治疗的优势。临床试验在 www.clinicaltrials.gov 注册（NCT02345161）。
