成人轻中度哮喘中布地奈德-福莫特罗按需使用对比布地奈德维持治疗联合按需使用特布他林治疗（PRACTICAL）：一项为期5
2020/02/11
成人轻中度哮喘中布地奈德-福莫特罗按需使用对比布地奈德维持治疗联合按需使用特布他林治疗（PRACTICAL）：一项为期52周，开放标签，多中心，优效性的随机对照试验
摘要 背景：在患有轻度哮喘的成人中，与短效β-激动剂（SABA）缓解疗法相比，吸入皮质类固醇与快速起效的长效β-激动剂（LABA）的联合制剂作为缓解剂可减少哮喘的重度急性加重风险。我们比较了布地奈德-福莫特罗联合制剂作为缓解治疗与布地奈德维持加按需使用特布他林治疗的疗效差异。
方法：我们在新西兰的15个初级保健或医院临床试验单位和初级保健实践中进行了一项为期52周的非盲、平行、多中心，优效性的随机对照试验。参与者是18-75岁的成年人，他们自我报告且被医生诊断为哮喘，无论是否使用低至中等剂量的吸入糖皮质激素，他们在过去的12周内都使用了SABA来缓解症状。我们按1:1随机分配参与者联合吸入布地奈德200μg-福莫特罗6μg (按需吸入一吸)或联合使用布地奈德200μg/次 (每天两次吸入) 维持治疗+特布他林250μg (按需吸入两吸)。参与者和调查人员在非盲状态下进行小组分配;统计学家不知情分组情况并分析主要结果。我们在第4周、第16周、第28周、第40周和第52周安排了6次随机性研究访问。主要评定指标是按治疗意愿分析的每位患者每年的严重加重次数（严重恶化的定义为:因哮喘使用全身皮质类固醇至少3天，或因哮喘需要全身皮质类固醇而入院或急诊）。安全性分析包括接受至少一剂研究治疗药物的所有参与者。
结果：从2016年5月4日至2017年12月22日期间，我们将890名受试者分入治疗组，并纳入了885名合格受试者：437名布地奈德-福莫特罗（按需）和448名布地奈德维持和特布他林（按需）。布地奈德-福莫特罗按需使用的患者每人每年的严重加重低于布地奈德维持加特布他林按需使用的患者（每个病人每年的绝对率0.119 vs 0.172；相对率0.69，95％CI 0.48-1.00； p = 0.049）。 鼻咽炎是两组中最常见的不良事件，在440名接受布地奈德-福莫特罗治疗的患者中，有154名患者（35％）出现鼻咽炎，而在接受布地奈德维持加特布他林按需治疗的448名患者中有144名（32％）患者出现鼻咽炎。
讨论：在患有轻度至中度哮喘的成年人中，按需使用布地奈德-福莫特罗来缓解症状，比低剂量布地奈德维持加按需使用特布他林可以更有效地预防哮喘的重度急性加重。这些结果支持“2019年全球哮喘倡议”的建议，即对于轻度哮喘患者，吸入糖皮质激素-福莫特罗缓解疗法可以作为一种替代每日低剂量吸入糖皮质激素治疗方案。
（ 中国医科大学附属第一医院 李文扬 摘译 杨冬 审校）
（Jo Hardy, et al. Lancet. 2019 Aug 23）
Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, multicentre, superiority, randomised controlled trialJo Hardy, et al. Lancet. 2019 Aug 23
Abstract
BACKGROUND: In adults with mild asthma, a combination of an inhaled corticosteroid with a fast-onset long-acting β-agonist (LABA) used as reliever monotherapy reduces severe exacerbations compared with short-acting β-agonist (SABA) reliever therapy. We investigated the efficacy of combination budesonide-formoterol reliever therapy compared with maintenance budesonide plus as-needed terbutaline.
METHODS: We did a 52-week, open-label, parallel-group, multicentre, superiority, randomised controlled trial at 15 primary care or hospital-based clinical trials units and primary care practices in New Zealand. Participants were adults aged 18-75 years with a self-reported doctor's diagnosis of asthma who were using SABA for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids in the previous 12 weeks. We randomly assigned participants (1:1) to either reliever therapy with budesonide 200 μg-formoterol 6 μg Turbuhaler (one inhalation as needed for relief of symptoms) or maintenance budesonide 200 μg Turbuhaler (one inhalation twice daily) plus terbutaline 250 μg Turbuhaler (two inhalations as needed). Participants and investigators were not masked to group assignment; the statistician was masked for analysis of the primary outcome. Six study visits were scheduled: randomisation, and weeks 4, 16, 28, 40, and 52. The primary outcome was the number of severe exacerbations per patient per year analysed by intention to treat (severe exacerbations defined as use of systemic corticosteroids for at least 3 days because of asthma, or admission to hospital or an emergency department visit because of asthma requiring systemic corticosteroids). Safety analyses included all participants who had received at least one dose of study treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616000377437.
FINDINGS: Between May 4, 2016, and Dec 22, 2017, we assigned 890 participants to treatment and included 885 eligible participants in the analysis: 437 assigned to budesonide-formoterol as needed and 448 to budesonide maintenance plus terbutaline as needed. Severe exacerbations per patient per year were lower with as-needed budesonide-formoterol than with maintenance budesonide plus terbutaline as needed (absolute rate per patient per year 0·119 vs 0·172; relative rate 0·69, 95% CI 0·48-1·00; p=0·049). Nasopharyngitis was the most common adverse event in both groups, occurring in 154 (35%) of 440 patients receiving as-needed budesonide-formoterol and 144 (32%) of 448 receiving maintenance budesonide plus terbutaline as needed.
INTERPRETATION: In adults with mild to moderate asthma, budesonide-formoterol used as needed for symptom relief was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline. The findings support the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid-formoterol reliever therapy is an alternative regimen to daily low-dose inhaled corticosteroid for patients with mild asthma.
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