丙酸氟替卡松/富马酸福莫特罗在儿科哮喘患者中的疗效和安全性：一项随机对照试验。

Efficacy and safety of fluticasone propionate/formoterol fumarate in pediatric asthma patients: a randomized controlled trial.

机构信息

Prywatna Praktyka Lekarska, Gabinet Pediatryczno-Alergologiczny, Ul. Przejazd 2A, Białystok, Poland.

University Hospital Plovdiv, Medical University of Plovdiv, Bulgaria.

出版信息

Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618777924. doi: 10.1177/1753466618777924.

BACKGROUND

The efficacy and safety of fluticasone propionate/formoterol fumarate pressurized metered-dose inhaler (pMDI) (fluticasone/formoterol; Flutiform; 100/10 µg b.i.d.) was compared with fluticasone propionate (Flixotide Evohaler pMDI; 100 µg b.i.d.) and fluticasone/salmeterol (Seretide Evohaler pMDI; 100/50 µg b.i.d.) in a pediatric asthma population (EudraCT number: 2010-024635-16).

METHODS

A double-blind, double-dummy, parallel group, multicenter study. Patients, aged 5-<12 years with persistent asthma ⩾ 6 months and forced expiratory volume in 1 s (FEV) ⩽ 90% predicted were randomized 1:1:1 to 12 weeks' treatment. The study objectives were to demonstrate superiority of fluticasone/formoterol to fluticasone and non-inferiority to fluticasone/salmeterol.

RESULTS

A total of 512 patients were randomized: fluticasone/formoterol, 169; fluticasone, 173; fluticasone/salmeterol, 170. Fluticasone/formoterol was superior to fluticasone for the primary endpoint: change from predose FEV at baseline to 2 h postdose FEV over 12 weeks [least squares (LS) mean difference 0.07 l; 95% confidence interval (CI) 0.03, 0.11; p < 0.001] and the first key secondary endpoint, FEV area under the curve over 4 hours (AUC) at week 12 (LS mean difference 0.09 l; 95% CI: 0.04, 0.13; p < 0.001). Per a prespecified non-inferiority margin of -0.1 l, fluticasone/formoterol was non-inferior to fluticasone/salmeterol for the primary endpoint (LS mean difference 0.00 l; 95% CI -0.04, 0.04; p < 0.001) and first key secondary endpoint (LS mean difference 0.01; 95% CI -0.03, 0.06; p < 0.001). Fluticasone/formoterol was non-inferior to fluticasone/salmeterol for the second key secondary endpoint, change from predose FEV over 12 weeks (treatment difference -0.02 l; 95% CI -0.06, 0.02; p < 0.001), but was not superior to fluticasone for this endpoint (LS mean difference 0.03 l; 95% CI -0.01, 0.07; p = 0.091). All treatments elicited large improvements from baseline to week 12 for the Pediatric Asthma Quality of Life Questionnaire (LS mean change 0.76 to 0.85 units) and Asthma Control Questionnaire (LS mean change -1.03 to -1.13 units). Few severe exacerbations were seen (fluticasone/formoterol: two; fluticasone/salmeterol: two). All treatments were well tolerated.

CONCLUSIONS

This study supports the efficacy and safety of fluticasone/formoterol in a pediatric asthma population and its superiority to fluticasone.

背景

丙酸氟替卡松/福莫特罗富马酸盐定量吸入器（pMDI）（丙酸氟替卡松/福莫特罗；Flutiform；100/10μg，每日 2 次）的疗效和安全性已在儿科哮喘人群中与丙酸氟替卡松（Flixotide Evohaler pMDI；100μg，每日 2 次）和氟替卡松/沙美特罗（Seretide Evohaler pMDI；100/50μg，每日 2 次）进行了比较（EudraCT 编号：2010-024635-16）。

方法

一项双盲、双模拟、平行组、多中心研究。年龄为 5-<12 岁、持续哮喘时间 ⩾ 6 个月且第 1 秒用力呼气量（FEV） ⩽ 90%预计值的患者按 1:1:1 的比例随机分为 12 周的治疗组。研究目的是证明丙酸氟替卡松/福莫特罗优于丙酸氟替卡松且非劣效于氟替卡松/沙美特罗。

结果

共有 512 名患者被随机分组：丙酸氟替卡松/福莫特罗组 169 例，丙酸氟替卡松组 173 例，氟替卡松/沙美特罗组 170 例。与丙酸氟替卡松相比，丙酸氟替卡松/福莫特罗在主要终点（从基线时的预剂量 FEV 到 12 周时的 2 小时后 FEV）和第 12 周时的 FEV 4 小时曲线下面积（AUC）的第一个关键次要终点方面具有优势[最小二乘（LS）均值差异 0.07 l；95%置信区间（CI）0.03，0.11；p < 0.001]和第 12 周时的 FEV AUC（LS 均值差异 0.09 l；95%CI：0.04，0.13；p < 0.001）。根据预先设定的非劣效性边界-0.1 l，丙酸氟替卡松/福莫特罗在主要终点（LS 均值差异 0.00 l；95%CI：-0.04，0.04；p < 0.001）和第一个关键次要终点（LS 均值差异 0.01；95%CI：-0.03，0.06；p < 0.001）方面非劣效于氟替卡松/沙美特罗。丙酸氟替卡松/福莫特罗在从基线到 12 周的 FEV 变化方面也非劣效于氟替卡松/沙美特罗（治疗差异-0.02 l；95%CI：-0.06，0.02；p < 0.001），但在该终点方面并不优于丙酸氟替卡松（LS 均值差异 0.03 l；95%CI：-0.01，0.07；p = 0.091）。所有治疗组在第 12 周时都从基线水平显著改善了儿童哮喘生活质量问卷（LS 平均变化 0.76 到 0.85 单位）和哮喘控制问卷（LS 平均变化-1.03 到-1.13 单位）。很少有严重的恶化（丙酸氟替卡松/福莫特罗：2 例；氟替卡松/沙美特罗：2 例）。所有治疗均具有良好的耐受性。