意大利费拉拉大学医学院Alberto Papi团队研究了吸入沙丁胺醇-布地奈德固定剂量组合抢救哮喘患者的疗效。该研究于2022年5月15日发表在《新英格兰医学杂志》上。

当哮喘症状恶化时，患者通常依赖短效β2-激动剂（SABA）抢救治疗，但SABA不能解决炎症恶化问题，这会使患者面临严重哮喘恶化的风险。与单独使用沙丁胺醇相比，使用沙丁胺醇和布地奈德的固定剂量组合作为抢救药物有望降低严重哮喘恶化的风险。

研究组进行了一项多国、临床3期、双盲、随机、事件驱动的试验，以评估沙丁胺醇-布地奈德与单独沙丁胺醇作为抢救药物对接受吸入糖皮质激素维持治疗的中重度哮喘患者的疗效和安全性，并在整个试验过程中持续进行。

研究组招募成人和青少年（≥12岁）中重度哮喘患者，按1:1:1的比例随机分配至三个试验组中的一个：分别接受180μg沙丁胺醇和160μg布地奈德的固定剂量组合（高剂量组合组），180μg沙丁胺醇和80μg布地奈德的固定剂量组合（低剂量组合组），或180μg沙丁胺醇（沙丁胺醇单独组）。将4至11岁的儿童随机分为低剂量联合用药组或沙丁胺醇单独用药组。主要疗效终点为在意向治疗人群中进行的时间-事件分析中首次严重哮喘恶化事件。

共有3132名患者接受了随机分组，其中97%为12岁及以上。与沙丁胺醇单用组相比，高剂量联合用药组严重哮喘恶化的风险显著降低26%，危险比为0.74。与单用沙丁胺醇组相比，低剂量联合用药组的危险比为0.84。三个试验组的不良事件发生率相似。

研究结果表明，在接受广泛吸入糖皮质激素维持治疗的中重度哮喘患者中，根据需要使用180μg沙丁胺醇和160μg布地奈德的固定剂量组合比根据需要单独使用沙丁胺醇可显著降低哮喘严重恶化的风险。

附：英文原文

Title: Albuterol–Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma | NEJM

Author: Alberto Papi, M.D.,, Bradley E. Chipps, M.D.,, Richard Beasley, D.Sc.,, Reynold A. Panettieri, Jr., M.D.,, Elliot Israel, M.D.,, Mark Cooper, M.Sc.,, Lynn Dunsire, M.Sc.,, Allison Jeynes-Ellis, M.D.,, Eva Johnsson, M.D.,, Robert Rees, Ph.D.,, Christy Cappelletti, Pharm.D.,, and Frank C. Albers, M.D.

Issue&Volume: 2022-05-15

Abstract:

Background

As asthma symptoms worsen, patients typically rely on short-acting β2-agonist (SABA) rescue therapy, but SABAs do not address worsening inflammation, which leaves patients at risk for severe asthma exacerbations. The use of a fixed-dose combination of albuterol and budesonide, as compared with albuterol alone, as rescue medication might reduce the risk of severe asthma exacerbation.

Methods

We conducted a multinational, phase 3, double-blind, randomized, event-driven trial to evaluate the efficacy and safety of albuterol–budesonide, as compared with albuterol alone, as rescue medication in patients with uncontrolled moderate-to-severe asthma who were receiving inhaled glucocorticoid-containing maintenance therapies, which were continued throughout the trial. Adults and adolescents (≥12 years of age) were randomly assigned in a 1:1:1 ratio to one of three trial groups: a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide (with each dose consisting of two actuations of 90 μg and 80 μg, respectively [the higher-dose combination group]), a fixed-dose combination of 180 μg of albuterol and 80 μg of budesonide (with each dose consisting of two actuations of 90 μg and 40 μg, respectively [the lower-dose combination group]), or 180 μg of albuterol (with each dose consisting of two actuations of 90 μg [the albuterol-alone group]). Children 4 to 11 years of age were randomly assigned to only the lower-dose combination group or the albuterol-alone group. The primary efficacy end point was the first event of severe asthma exacerbation in a time-to-event analysis, which was performed in the intention-to-treat population.

Results

A total of 3132 patients underwent randomization, among whom 97% were 12 years of age or older. The risk of severe asthma exacerbation was significantly lower, by 26%, in the higher-dose combination group than in the albuterol-alone group (hazard ratio, 0.74; 95% confidence interval [CI], 0.62 to 0.89; P=0.001). The hazard ratio in the lower-dose combination group, as compared with the albuterol-alone group, was 0.84 (95% CI, 0.71 to 1.00; P=0.052). The incidence of adverse events was similar in the three trial groups.

Conclusions

The risk of severe asthma exacerbation was significantly lower with as-needed use of a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide than with as-needed use of albuterol alone among patients with uncontrolled moderate-to-severe asthma who were receiving a wide range of inhaled glucocorticoid-containing maintenance therapies.

DOI: 10.1056/NEJMoa2203163

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2203163