轻度哮喘患者按需吸入布地奈德 -福莫特罗VS布地奈德维持治疗的比较
2018/08/16
摘要
背景：轻度哮喘患者通常依赖吸入短效β2受体激动剂来缓解症状，对维持治疗的依从性较差。有些患者则是按需使用支气管舒张剂与糖皮质激素复合制剂以缓解症状并降低急性加重风险。
方法：我们进行了一项为期52周的双盲多中心试验，该试验入组12岁或以上患有轻度哮喘并且可以接受常规吸入糖皮质激素治疗的患者。患者被随机分配接受每日两次安慰剂加按需使用布地奈德 - 福莫特罗（200ug布地奈德和6ug福莫特罗）或每日两次布地奈德（200ug）加按需使用特布他林（0.5 mg）。 初步分析比较了布地奈德 - 福莫特罗按需治疗组与布地奈德维持治疗组年化急性发作次数，预先设定的非劣效性限值为1.2。 根据哮喘控制问卷-5（ACQ-5）的评分，从0（无损伤）到6（最大损害）的等级评估症状。
结果：共有4215名患者接受随机分组，4176例（布地奈德 - 福莫特罗组2089例，布地奈德维持组2087例）纳入完整分析组。布地奈德福莫特罗按需治疗组哮喘急性发作发生率不劣于布地奈德维持治疗组；年化急性发作发生率分别为0.11（95％可信区间[CI]，0.10至0.13）和0.12（95％CI，0.10至0.14）（RR，0.97；单侧95％CI，1.16）。 布地奈德 - 福莫特罗组（66ug）的每日吸入糖皮质激素剂量中位数低于布地奈德维持组（267ug）。两组距第一次急性发作的时间相似（HR，0.96; 95％CI，0.78至1.17）。布地奈德维持治疗组 ACQ-5评分高于布地奈德福莫特罗按需治疗组0.11单位（95％CI，0.07-0.15）。
结论：轻度哮喘的患者在治疗52周后，布地奈德 - 福莫特罗按需治疗组的哮喘急性发作发生率不劣于布地奈德维持治疗组，但其在症状控制方面较差。 布地奈德 - 福莫特罗组患者吸入糖皮质激素量约为布地奈德维持组的四分之一。
Bateman ED et al. N Engl J Med. 2018 May 17
Abstract
Background：Patients with mild asthma often rely on inhaled short-acting β2-agonists for symptom relief and have poor adherence to maintenance therapy. Another approach might be for patients to receive a fast-acting reliever plus an inhaled glucocorticoid component on an as-needed basis to address symptoms and exacerbation risk.
Methods：We conducted a 52-week, double-blind, multicenter trial involving patients 12 years of age or older who had mild asthma and were eligible for treatment with regular inhaled glucocorticoids. Patients were randomly assigned to receive twice-daily placebo plus budesonide–formoterol (200 μg of budesonide and 6 μg of formoterol) used as needed or budesonide maintenance therapy with twice-daily budesonide (200 μg)plus terbutaline (0.5 mg) used as needed. The primary analysis compared budesonide– formoterol used as needed with budesonide maintenance therapy with regard to the annualized rate of severe exacerbations, with a prespecified noninferiority limit of 1.2. Symptoms were assessed according to scores on the Asthma Control Questionnaire–5 (ACQ-5) on a scale from 0 (no impairment) to 6 (maximum impairment).
Results：A total of 4215 patients underwent randomization, and 4176 (2089 in the budesonide–formoterol group and 2087 in the budesonide maintenance group) were included in the full analysis set. Budesonide formoterol used as needed was noninferior to budesonide maintenance therapy for severe exacerbations; the annualized rate of severe exacerbations was 0.11 (95% confidence interval [CI], 0.10 to 0.13) and 0.12(95% CI, 0.10 to 0.14), respectively (rate ratio, 0.97; upper one-sided 95% confidence limit, 1.16). The median daily metered dose of inhaled glucocorticoid was lower in the budesonide–formoterol group (66 μg) than in the budesonide maintenance group (267 μg). The time to the first exacerbation was similar in the two groups (hazard ratio, 0.96; 95% CI, 0.78 to 1.17). The change in ACQ-5 score showed a difference of 0.11 units (95% CI, 0.07 to 0.15) in favor of budesonide maintenance therapy.
Conclusions：In patients with mild asthma, budesonide–formoterol used as needed was noninferior to twice-daily budesonide with respect to the rate of severe asthma exacerbations during 52 weeks of treatment but was inferior in controlling symptoms. Patients in the budesonide–formoterol group had approximately one quarter of the inhaled glucocorticoid exposure of those in the budesonide maintenance group.
背景：轻度哮喘患者通常依赖吸入短效β2受体激动剂来缓解症状，对维持治疗的依从性较差。有些患者则是按需使用支气管舒张剂与糖皮质激素复合制剂以缓解症状并降低急性加重风险。
方法：我们进行了一项为期52周的双盲多中心试验，该试验入组12岁或以上患有轻度哮喘并且可以接受常规吸入糖皮质激素治疗的患者。患者被随机分配接受每日两次安慰剂加按需使用布地奈德 - 福莫特罗（200ug布地奈德和6ug福莫特罗）或每日两次布地奈德（200ug）加按需使用特布他林（0.5 mg）。 初步分析比较了布地奈德 - 福莫特罗按需治疗组与布地奈德维持治疗组年化急性发作次数，预先设定的非劣效性限值为1.2。 根据哮喘控制问卷-5（ACQ-5）的评分，从0（无损伤）到6（最大损害）的等级评估症状。
结果：共有4215名患者接受随机分组，4176例（布地奈德 - 福莫特罗组2089例，布地奈德维持组2087例）纳入完整分析组。布地奈德福莫特罗按需治疗组哮喘急性发作发生率不劣于布地奈德维持治疗组；年化急性发作发生率分别为0.11（95％可信区间[CI]，0.10至0.13）和0.12（95％CI，0.10至0.14）（RR，0.97；单侧95％CI，1.16）。 布地奈德 - 福莫特罗组（66ug）的每日吸入糖皮质激素剂量中位数低于布地奈德维持组（267ug）。两组距第一次急性发作的时间相似（HR，0.96; 95％CI，0.78至1.17）。布地奈德维持治疗组 ACQ-5评分高于布地奈德福莫特罗按需治疗组0.11单位（95％CI，0.07-0.15）。
结论：轻度哮喘的患者在治疗52周后，布地奈德 - 福莫特罗按需治疗组的哮喘急性发作发生率不劣于布地奈德维持治疗组，但其在症状控制方面较差。 布地奈德 - 福莫特罗组患者吸入糖皮质激素量约为布地奈德维持组的四分之一。
（复旦大学附属中山医院呼吸内科 包晨 摘译 杨冬 审校）
（Bateman ED et al. N Engl J Med. 2018 May 17）
As-Needed Budesonide–Formoterol versus Maintenance Budesonide in Mild Asthma（Bateman ED et al. N Engl J Med. 2018 May 17）
Bateman ED et al. N Engl J Med. 2018 May 17
Abstract
Background：Patients with mild asthma often rely on inhaled short-acting β2-agonists for symptom relief and have poor adherence to maintenance therapy. Another approach might be for patients to receive a fast-acting reliever plus an inhaled glucocorticoid component on an as-needed basis to address symptoms and exacerbation risk.
Methods：We conducted a 52-week, double-blind, multicenter trial involving patients 12 years of age or older who had mild asthma and were eligible for treatment with regular inhaled glucocorticoids. Patients were randomly assigned to receive twice-daily placebo plus budesonide–formoterol (200 μg of budesonide and 6 μg of formoterol) used as needed or budesonide maintenance therapy with twice-daily budesonide (200 μg)plus terbutaline (0.5 mg) used as needed. The primary analysis compared budesonide– formoterol used as needed with budesonide maintenance therapy with regard to the annualized rate of severe exacerbations, with a prespecified noninferiority limit of 1.2. Symptoms were assessed according to scores on the Asthma Control Questionnaire–5 (ACQ-5) on a scale from 0 (no impairment) to 6 (maximum impairment).
Results：A total of 4215 patients underwent randomization, and 4176 (2089 in the budesonide–formoterol group and 2087 in the budesonide maintenance group) were included in the full analysis set. Budesonide formoterol used as needed was noninferior to budesonide maintenance therapy for severe exacerbations; the annualized rate of severe exacerbations was 0.11 (95% confidence interval [CI], 0.10 to 0.13) and 0.12(95% CI, 0.10 to 0.14), respectively (rate ratio, 0.97; upper one-sided 95% confidence limit, 1.16). The median daily metered dose of inhaled glucocorticoid was lower in the budesonide–formoterol group (66 μg) than in the budesonide maintenance group (267 μg). The time to the first exacerbation was similar in the two groups (hazard ratio, 0.96; 95% CI, 0.78 to 1.17). The change in ACQ-5 score showed a difference of 0.11 units (95% CI, 0.07 to 0.15) in favor of budesonide maintenance therapy.
Conclusions：In patients with mild asthma, budesonide–formoterol used as needed was noninferior to twice-daily budesonide with respect to the rate of severe asthma exacerbations during 52 weeks of treatment but was inferior in controlling symptoms. Patients in the budesonide–formoterol group had approximately one quarter of the inhaled glucocorticoid exposure of those in the budesonide maintenance group.
