Background

The efficacy and safety of once-daily (o.d.) fixed-dose combination of indacaterol (IND), glycopyrronium (GLY) and mometasone furoate (MF) via Breezhaler® versus concurrent administration of salmeterol/fluticasone (SAL/FLU) twice-daily (b.i.d.) via Accuhaler®+Tiotropium (TIO) o.d. via Respimat® was evaluated in patients with uncontrolled asthma.

Methods

Patients (aged ≥18 years), symptomatic (Asthma Control Questionnaire [ACQ]-7 ≥1.5) despite treatment with long-acting β₂-agonist/inhaled corticosteroid medium- or high-dose, received IND/GLY/MF high- (150/50/160 μg) or medium-dose (150/50/80 μg) o.d. or SAL/FLU high-dose (50/500 μg) b.i.d.+Tio 5 μg o.d. for 24 weeks. The primary objective was to confirm the non-inferiority of either dose of IND/GLY/MF to SAL/FLU high dose + TIO in terms of Asthma Quality of Life Questionnaire (AQLQ). Additional endpoints: ACQ-7, lung function, health status (St George's Respiratory Questionnaire [SGRQ]), exacerbations, and safety after 24 weeks.

Results

IND/GLY/MF high- and medium-dose met the primary endpoint, confirming non-inferiority to SAL/FLU high dose + TIO for AQLQ (least square mean treatment difference [Δ]: 0.073 and −0.038, respectively; both p < 0.001). IND/GLY/MF high-dose improved ACQ-7 (Δ: −0.124; p = 0.004), trough FEV₁ (Δ: 96 mL; p < 0.001), peak expiratory flow (morning [Δ: 9.56 L/min; p = 0.005], evening [Δ: 9.15 L/min; p = 0.006]) and SGRQ (Δ: −2.00; p = 0.04) versus SAL/FLU high dose + TIO. Improvements in these endpoints were comparable for IND/GLY/MF medium-dose and SAL/FLU high dose + TIO. Adverse events were generally comparable across treatments.

Conclusions

IND/GLY/MF high- and medium-dose o.d. via a single inhaler were non-inferior to SAL/FLU high-dose b.i.d. + TIO o.d. via two inhalers for AQLQ. IND/GLY/MF high-dose o.d. improved lung function, asthma control and health status versus SAL/FLU high dose + TIO, while IND/GLY/MF medium-dose had comparable efficacy but at a corresponding lower steroid dose.

中文翻译：

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对于不受控制的哮喘患者，固定剂量联合使用茚达特罗/格隆铵/糠酸莫米松酮与沙美特罗/氟替卡松每天两次与噻托溴铵每天一次固定剂量组合：一项随机，IIIb期，非自卑性研究（ARGON）。

背景

通过Breezhaler®每日一次（od）固定剂量的茚达特罗（IND），格隆铵（GLY）和糠酸莫米松（MF）固定剂量联合使用与沙美特罗/氟替卡松（SAL / FLU）每天两次同时给药的疗效和安全性（在未控制的哮喘患者中评估了通过Accuhaler®+噻托铵（TIO）或通过Respimat®进行的评估。

方法

患者（年龄≥18岁），有症状的（哮喘控制问卷[ACQ] -7-≥1.5），尽管与长效β治疗₂ -激动剂/吸入皮质类固醇中或高剂量，接收IND / GLY / MF高（ 150/50/160μg）或中剂量（150/50/80μg）或SAL / FLU高剂量（50/500μg）bid + Tio 5μgOD持续24周。主要目标是确认哮喘生活质量调查表（AQLQ）相对于SAL / FLU高剂量+ TIO而言，IND / GLY / MF的任何剂量均不逊色。其他指标：ACQ-7，肺功能，健康状况（圣乔治呼吸问卷[SGRQ]），病情加重和24周后的安全性。

结果

IND / GLY / MF高剂量和中等剂量达到主要终点，证实AQLQ不逊于SAL / FLU高剂量+ TIO（最小二乘均方差[Δ]：分别为0.073和-0.038；两者p < 0.001）。IND / GLY / MF大剂量改良型ACQ-7（Δ：-0.124; p = 0.004），谷FEV ₁（Δ：96 mL; p <0.001），呼气峰值流量（早晨[Δ：9.56 L / min; p = 0.005]，晚上[Δ：9.15 L / min； p = 0.006]）和SGRQ（Δ：-2.00； p = 0.04）相对于SAL / FLU高剂量+ TIO。这些终点的改善与IND / GLY / MF中剂量和SAL / FLU高剂量+ TIO相当。不良事件在各治疗之间通常具有可比性。

结论

通过一个吸入器获得的IND / GLY / MF高剂量和中等剂量OD不亚于通过两个吸入器获得的SAL / FLU高剂量bid + TIO OD。与高剂量SAL / FLU + TIO相比，高剂量IND / GLY / MF改善了肺功能，哮喘控制和健康状况，而中等剂量的IND / GLY / MF具有相同的疗效，但相应地降低了类固醇剂量。