轻度哮喘患者沙丁胺醇-布地奈德按需用药
2025/06/27
摘要
背景：在中至重度哮喘患者中，与沙丁胺醇单独按需用药相比，沙丁胺醇-布地奈德按需用药可显著降低重度哮喘发作风险。我们需要关于沙丁胺醇-布地奈德治疗轻度哮喘的数据。
方法：我们开展了一项完全虚拟、分散、3b期、多中心、双盲、事件驱动的试验，纳入≥12岁的轻度哮喘患者，这些患者接受短效β2受体激动剂（SABA）（联用或不联用小剂量吸入型糖皮质激素或白三烯受体拮抗剂）治疗后仍未得到控制。我们以1∶1的比例将参与者随机分组，分别按需接受180 μg沙丁胺醇和160 μg布地奈德（每一剂量包括两个吸入器驱动，分别为90 μg和80 μg）或180 μg沙丁胺醇（每一剂量包括两个吸入器驱动，分别为90 μg）治疗，为期长达52周。主要终点是在至事件发生的时间分析中，在治疗有效人群中评估的首次哮喘重度发作，关键次要终点是意向治疗人群中的首次重度发作。次要终点包括哮喘重度发作的年发生率和全身性糖皮质激素暴露。
结果：共有2516名参与者接受了随机分组。1,797例（71.4%）完成试验。在全分析人群的2,421例参与者（沙丁胺醇-布地奈德组1,207例，沙丁胺醇组1,212例）中，97.2%的参与者年龄≥18岁。基线时74.4%使用SABA单药治疗。在预设的期中分析时，本试验因疗效而终止。在治疗有效人群中，沙丁胺醇-布地奈德组5.1%的参与者和沙丁胺醇组9.1%的参与者发生了重度加重（风险比，0.53;p < 0.05）。95% CI, 0.39 ~ 0.73)和5.3%和9.4%(风险比，0.54；95% CI, 0.40 ~ 0.73)（两项比较的P<0.001）。沙丁胺醇-布地奈德组的年哮喘重度发作率低于沙丁胺醇组(0.15 vs. 0.32；率比0.47；95% CI, 0.34 ~ 0.64)，以及全身性糖皮质激素的平均年总剂量（每年23.2 mg vs. 61.9 mg）也是如此。两个治疗组的不良事件相似。
结论：在轻度哮喘患者中，与沙丁胺醇单独按需用药相比，沙丁胺醇-布地奈德按需用药降低了哮喘重度发作的风险。
As-Needed Albuterol-Budesonide in Mild Asthma
Craig LaForce, Frank Albers, Anna Danilewicz, Allison Jeynes-Ellis, Monica Kraft, Reynold A Panettieri Jr, Robert Rees, Samuel Bardsley, Lynn Dunsire, Tim Harrison, Olami Sobande, Raulin Surujbally, Frank Trudo, Christy Cappelletti, Alberto Papi, Richard Beasley, Bradley E Chipps, Elliot Israel, Hitesh Pandya, Martin Clancy, Leonard B Bacharier; BATURA Investigators
Abstract
Background:As-needed use of albuterol-budesonide has been shown to result in a significantly lower risk of severe asthma exacerbation than as-needed use of albuterol alone among patients with moderate-to-severe asthma. Data on albuterol-budesonide in mild asthma are needed.
Methods:We conducted a fully virtual, decentralized, phase 3b, multicenter, double-blind, event-driven trial involving persons 12 years of age or older with disease that was uncontrolled despite treatment for mild asthma with a short-acting β2-agonist (SABA) with or without a low-dose inhaled glucocorticoid or leukotriene-receptor antagonist. Participants were randomly assigned in a 1:1 ratio to a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide (with each dose consisting of two inhaler actuations of 90 μg and 80 μg, respectively) or 180 μg of albuterol (with each dose consisting of two inhaler actuations of 90 μg) on an as-needed basis for up to 52 weeks. The primary end point was the first severe asthma exacerbation, assessed in a time-to-event analysis, in the on-treatment efficacy population, and the key secondary end point was the first severe exacerbation in the intention-to-treat population. Secondary end points included the annualized rate of severe asthma exacerbations and exposure to systemic glucocorticoids.
Results:A total of 2516 participants underwent randomization; 1797 (71.4%) completed the trial. Of 2421 participants in the full analysis population (1209 assigned to the albuterol-budesonide group and 1212 to the albuterol group), 97.2% were 18 years of age or older; 74.4% used a SABA alone at baseline. The trial was stopped for efficacy at a prespecified interim analysis. A severe exacerbation occurred in 5.1% of the participants in the albuterol-budesonide group and in 9.1% of those in the albuterol group in the on-treatment efficacy population (hazard ratio, 0.53; 95% confidence interval [CI], 0.39 to 0.73) and in 5.3% and 9.4%, respectively, in the intention-to-treat population (hazard ratio, 0.54; 95% CI, 0.40 to 0.73) (P<0.001 for both comparisons). The annualized rate of severe asthma exacerbations was lower with albuterol-budesonide than with albuterol (0.15 vs. 0.32; rate ratio, 0.47; 95% CI, 0.34 to 0.64), as was the mean annualized total dose of systemic glucocorticoids (23.2 vs. 61.9 mg per year). Adverse events were similar in the two treatment groups.
Conclusions:As-needed use of albuterol-budesonide resulted in a lower risk of a severe asthma exacerbation than as-needed use of albuterol alone among participants with disease that was uncontrolled despite treatment for mild asthma.
背景：在中至重度哮喘患者中，与沙丁胺醇单独按需用药相比，沙丁胺醇-布地奈德按需用药可显著降低重度哮喘发作风险。我们需要关于沙丁胺醇-布地奈德治疗轻度哮喘的数据。
方法：我们开展了一项完全虚拟、分散、3b期、多中心、双盲、事件驱动的试验，纳入≥12岁的轻度哮喘患者，这些患者接受短效β2受体激动剂（SABA）（联用或不联用小剂量吸入型糖皮质激素或白三烯受体拮抗剂）治疗后仍未得到控制。我们以1∶1的比例将参与者随机分组，分别按需接受180 μg沙丁胺醇和160 μg布地奈德（每一剂量包括两个吸入器驱动，分别为90 μg和80 μg）或180 μg沙丁胺醇（每一剂量包括两个吸入器驱动，分别为90 μg）治疗，为期长达52周。主要终点是在至事件发生的时间分析中，在治疗有效人群中评估的首次哮喘重度发作，关键次要终点是意向治疗人群中的首次重度发作。次要终点包括哮喘重度发作的年发生率和全身性糖皮质激素暴露。
结果：共有2516名参与者接受了随机分组。1,797例（71.4%）完成试验。在全分析人群的2,421例参与者（沙丁胺醇-布地奈德组1,207例，沙丁胺醇组1,212例）中，97.2%的参与者年龄≥18岁。基线时74.4%使用SABA单药治疗。在预设的期中分析时，本试验因疗效而终止。在治疗有效人群中，沙丁胺醇-布地奈德组5.1%的参与者和沙丁胺醇组9.1%的参与者发生了重度加重（风险比，0.53;p < 0.05）。95% CI, 0.39 ~ 0.73)和5.3%和9.4%(风险比，0.54；95% CI, 0.40 ~ 0.73)（两项比较的P<0.001）。沙丁胺醇-布地奈德组的年哮喘重度发作率低于沙丁胺醇组(0.15 vs. 0.32；率比0.47；95% CI, 0.34 ~ 0.64)，以及全身性糖皮质激素的平均年总剂量（每年23.2 mg vs. 61.9 mg）也是如此。两个治疗组的不良事件相似。
结论：在轻度哮喘患者中，与沙丁胺醇单独按需用药相比，沙丁胺醇-布地奈德按需用药降低了哮喘重度发作的风险。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
（N Engl J Med. 2025 May 19. doi: 10.1056/NEJMoa2504544.）
As-Needed Albuterol-Budesonide in Mild Asthma
Craig LaForce, Frank Albers, Anna Danilewicz, Allison Jeynes-Ellis, Monica Kraft, Reynold A Panettieri Jr, Robert Rees, Samuel Bardsley, Lynn Dunsire, Tim Harrison, Olami Sobande, Raulin Surujbally, Frank Trudo, Christy Cappelletti, Alberto Papi, Richard Beasley, Bradley E Chipps, Elliot Israel, Hitesh Pandya, Martin Clancy, Leonard B Bacharier; BATURA Investigators
Abstract
Background:As-needed use of albuterol-budesonide has been shown to result in a significantly lower risk of severe asthma exacerbation than as-needed use of albuterol alone among patients with moderate-to-severe asthma. Data on albuterol-budesonide in mild asthma are needed.
Methods:We conducted a fully virtual, decentralized, phase 3b, multicenter, double-blind, event-driven trial involving persons 12 years of age or older with disease that was uncontrolled despite treatment for mild asthma with a short-acting β2-agonist (SABA) with or without a low-dose inhaled glucocorticoid or leukotriene-receptor antagonist. Participants were randomly assigned in a 1:1 ratio to a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide (with each dose consisting of two inhaler actuations of 90 μg and 80 μg, respectively) or 180 μg of albuterol (with each dose consisting of two inhaler actuations of 90 μg) on an as-needed basis for up to 52 weeks. The primary end point was the first severe asthma exacerbation, assessed in a time-to-event analysis, in the on-treatment efficacy population, and the key secondary end point was the first severe exacerbation in the intention-to-treat population. Secondary end points included the annualized rate of severe asthma exacerbations and exposure to systemic glucocorticoids.
Results:A total of 2516 participants underwent randomization; 1797 (71.4%) completed the trial. Of 2421 participants in the full analysis population (1209 assigned to the albuterol-budesonide group and 1212 to the albuterol group), 97.2% were 18 years of age or older; 74.4% used a SABA alone at baseline. The trial was stopped for efficacy at a prespecified interim analysis. A severe exacerbation occurred in 5.1% of the participants in the albuterol-budesonide group and in 9.1% of those in the albuterol group in the on-treatment efficacy population (hazard ratio, 0.53; 95% confidence interval [CI], 0.39 to 0.73) and in 5.3% and 9.4%, respectively, in the intention-to-treat population (hazard ratio, 0.54; 95% CI, 0.40 to 0.73) (P<0.001 for both comparisons). The annualized rate of severe asthma exacerbations was lower with albuterol-budesonide than with albuterol (0.15 vs. 0.32; rate ratio, 0.47; 95% CI, 0.34 to 0.64), as was the mean annualized total dose of systemic glucocorticoids (23.2 vs. 61.9 mg per year). Adverse events were similar in the two treatment groups.
Conclusions:As-needed use of albuterol-budesonide resulted in a lower risk of a severe asthma exacerbation than as-needed use of albuterol alone among participants with disease that was uncontrolled despite treatment for mild asthma.
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基于网络药理学与实验验证探讨喘可治注射液治疗哮喘的抗炎机制
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吸入性短效β2受体激动剂对学龄前儿童急性喘息/哮喘症状的短期疗效：一项系统评价与Meta分析
