Institute of Inflammation and Repair, University of Manchester, University Hospital of South Manchester, Manchester M23 9LT, UK.
BMC Pulm Med. 2014 Jul 9;14:113. doi: 10.1186/1471-2466-14-113.
Inhaled corticosteroids are a mainstay of therapy for persistent asthma, but suboptimal adherence with twice-daily use is widespread. Fluticasone furoate (FF) is a new inhaled corticosteroid (ICS) suitable for once-daily dosing in asthma. This study was performed to descriptively assess the efficacy and safety of two doses of FF, with no planned formal statistical hypothesis testing.
This was a 24-week double-blind, multicentre, parallel-group study (NCT01431950). Patients aged ≥ 12 years with moderate-severe persistent asthma and uncontrolled on mid-high dose ICS were stratified by baseline FEV1 and randomised (1:1) to treatment with FF 100 μg or 200 μg once daily in the evening. The primary endpoint was change from baseline trough FEV1 after 24 weeks; secondary and other endpoints included peak expiratory flow (PEF) and rescue-free and symptom-free 24-hour periods over Weeks 1-24, and Asthma Control Test™ (ACT) score at Week 24. A pre-specified subgroup analysis of patients by randomisation strata was performed for the primary and selected secondary and other endpoints. Safety assessments included adverse events, laboratory and vital sign measurements, and change from baseline in 24-hour urinary cortisol at Week 24.
With FF 100 μg and 200 μg, least squares mean trough FEV1 improved from baseline by 208 mL and 284 mL, respectively, at Week 24; treatment difference: 77 mL (95% CI: -39, 192). Similar improvements from baseline in rescue- and symptom-free periods, and morning and evening PEF were observed in both groups. Patients were 42% more likely to be well-controlled (ACT score ≥ 20) with FF 200 μg than with FF 100 μg. Slightly more patients receiving FF 200 μg vs. FF 100 μg reported adverse events (63% vs. 59%) and events deemed treatment related (5% vs. <1%). Seven serious adverse events (FF 200 μg 4; FF 100 μg 3) were reported, none of which were deemed treatment related. No clinically relevant effects of either dose on 24-hour urinary cortisol were observed.
Improvements from baseline in trough FEV1 were observed after 24 weeks of treatment with both doses of FF, with a numerically greater improvement in FEV1 observed in patients receiving FF 200 μg. Secondary endpoint findings were similar between groups. No safety concerns were identified during the study.
吸入性皮质类固醇是治疗持续性哮喘的主要药物，但每日两次使用的依从性不理想是普遍存在的。糠酸氟替卡松（FF）是一种新的吸入性皮质类固醇（ICS），适用于哮喘的每日一次给药。本研究旨在描述性评估两种剂量 FF 的疗效和安全性，未计划进行正式的统计假设检验。
这是一项为期 24 周的双盲、多中心、平行组研究（NCT01431950）。年龄≥12 岁、中重度持续性哮喘且中高剂量 ICS 控制不佳的患者按基线 FEV1 分层，并随机（1:1）接受 FF 100μg 或 200μg 每日一次在晚上治疗。主要终点是 24 周时的最低谷 FEV1 从基线的变化；次要和其他终点包括第 1-24 周的峰流速（PEF）和无抢救和无症状的 24 小时期，以及第 24 周的哮喘控制测试（ACT）评分。对随机分层患者进行了主要和选定的次要和其他终点的预先指定亚组分析。安全性评估包括不良事件、实验室和生命体征测量以及第 24 周时的 24 小时尿液皮质醇从基线的变化。
FF 100μg 和 200μg 治疗 24 周后，最低谷 FEV1 分别比基线增加 208mL 和 284mL；治疗差异：77mL（95%CI：-39,192）。两组患者的抢救和无症状期、早晨和傍晚 PEF 均从基线改善。与 FF 100μg 相比，接受 FF 200μg 治疗的患者有 42%更有可能得到良好控制（ACT 评分≥20）。与 FF 100μg 相比，接受 FF 200μg 治疗的患者报告的不良事件（63%对 59%）和认为与治疗相关的事件（5%对<1%）略多。报告了 7 例严重不良事件（FF 200μg 4 例；FF 100μg 3 例），均与治疗无关。两种剂量均未观察到对 24 小时尿液皮质醇有任何临床相关影响。
在接受 FF 两种剂量治疗 24 周后，最低谷 FEV1 从基线开始改善，接受 FF 200μg 治疗的患者的 FEV1 改善程度略大。两组的次要终点发现相似。在研究期间未发现安全性问题。
