近日，美国北卡罗来纳州临床研究所Craig LaForce团队研究了沙丁胺醇-布地奈德治疗轻度哮喘的疗效。相关论文于2025年5月19日发表在《新英格兰医学杂志》上。

在中度至重度哮喘患者中，按需使用沙丁胺醇-布地奈德比按需单独使用沙丁胺醇导致严重哮喘加重的风险显著降低。需要沙丁胺醇-布地奈德治疗轻度哮喘的数据。

研究组进行了一项完全虚拟、分散、多中心、双盲、事件驱动的3b期试验，纳入了12岁或以上的患者，尽管使用短效β2激动剂（SABA）联合或不联合低剂量吸入糖皮质激素或白三烯受体拮抗剂治疗轻度哮喘，但疾病仍未控制。参与者按1:1的比例随机分配到180 μg沙丁胺醇和160 μg布地奈德的固定剂量组合（每次剂量分别由两个吸入器驱动90 μg和80 μg组成）或180 μg沙丁胺醇（每次剂量由两个吸入器驱动90 μg），根据需要持续52周。主要终点是在治疗有效人群中第一次严重哮喘加重，通过时间-事件分析进行评估，关键的次要终点是在意向治疗人群中第一次严重哮喘加重。次要终点包括严重哮喘恶化的年化率和全身糖皮质激素暴露。

共有2516名受试者接受随机分组；1797例（71.4%）完成试验。在全部分析人群的2421名参与者中（沙丁胺醇-布地奈德组1209名，沙丁胺醇组1212名），97.2%的参与者年龄在18岁或以上；74.4%的人在基线时仅使用了SABA。在预先指定的中期分析中，试验因疗效而停止。沙丁胺醇-布地奈德组有5.1%的参与者发生严重恶化，沙丁胺醇组在治疗有效人群中有9.1%的参与者发生严重恶化(风险比，0.53；95%可信区间，0.39 ~ 0.73)，在意向治疗人群中分别为5.3%和9.4%(风险比，0.54；95% CI, 0.40 ~ 0.73)（两组比较P<均为0.001）。沙丁胺醇-布地奈德组哮喘严重发作的年化率低于沙丁胺醇组(0.15 vs. 0.32；比率比，0.47；95% CI, 0.34 - 0.64)，系统性糖皮质激素的平均年化总剂量（23.2 vs 61.9 mg /年）也是如此。两个治疗组的不良事件相似。

研究结果表明，根据需要使用沙丁胺醇-布地奈德导致严重哮喘恶化的风险低于根据需要单独使用沙丁胺醇的参与者，尽管轻度哮喘治疗不受控制。

附：英文原文

Title: As-Needed Albuterol–Budesonide in Mild Asthma

Author: 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

Issue&Volume: 2025-05-19

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.

DOI: NJ202505190000010

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2504544