沙美特罗替卡松干粉吸入剂（舒利迭）治疗哮喘。

Albuterol-Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma.

机构信息

From the Department of Respiratory Medicine, University of Ferrara Medical School, Ferrara, Italy (A.P.); the Capital Allergy and Respiratory Disease Center, Sacramento, CA (B.E.C.); the Medical Research Institute of New Zealand, Capital and Coast District Health Board, and Victoria University Wellington - all in Wellington, New Zealand (R.B.); Rutgers Institute for Translational Medicine and Science, Child Health Institute of New Jersey, Rutgers, the State University of New Jersey, New Brunswick (R.A.P.); Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); BioPharmaceuticals Research and Development, AstraZeneca, Cambridge (M.C., L.D.), and Avillion, London (A.J.-E., R.R.) - both in the United Kingdom; BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (E.J.); BioPharmaceuticals Research and Development, AstraZeneca, Durham, NC (C.C.); and Avillion, Northbrook, IL (F.C.A.).

出版信息

N Engl J Med. 2022 Jun 2;386(22):2071-2083. doi: 10.1056/NEJMoa2203163. Epub 2022 May 15.

DOI:10.1056/NEJMoa2203163

PMID:35569035

Abstract

BACKGROUND

As asthma symptoms worsen, patients typically rely on short-acting β-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. (Funded by Avillion; MANDALA ClinicalTrials.gov number, NCT03769090.).

摘要

背景

随着哮喘症状的恶化，患者通常依赖短效 β-激动剂（SABA）解救治疗，但 SABA 并不能解决恶化的炎症，这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解救药物可能会降低严重哮喘恶化的风险。

方法

我们进行了一项多中心、3 期、双盲、随机、事件驱动的试验，以评估沙丁胺醇-布地奈德固定剂量组合与单独使用沙丁胺醇作为解救药物在接受吸入性糖皮质激素维持治疗的未控制的中重度哮喘患者中的疗效和安全性，这些患者在整个试验过程中继续接受吸入性糖皮质激素维持治疗。成人和青少年（≥12 岁）按 1:1:1 的比例随机分配至以下三个试验组之一：沙丁胺醇 180μg 和布地奈德 160μg 的固定剂量组合（每种剂量由两剂 90μg 和 80μg 组成[高剂量组合组]），沙丁胺醇 180μg 和布地奈德 80μg 的固定剂量组合（每种剂量由两剂 90μg 和 40μg 组成[低剂量组合组]），或 180μg 沙丁胺醇（每剂由两剂 90μg 组成[沙丁胺醇单独组]）。4 至 11 岁的儿童仅随机分配至低剂量组合组或沙丁胺醇单独组。主要疗效终点是在时间事件分析中首次发生严重哮喘恶化的事件，该分析在意向治疗人群中进行。

结果

共有 3132 名患者接受了随机分组，其中 97%为 12 岁及以上。高剂量组合组严重哮喘恶化的风险显著降低 26%，与沙丁胺醇单独组相比（风险比，0.74；95%置信区间[CI]，0.62 至 0.89；P=0.001）。与沙丁胺醇单独组相比，低剂量组合组的风险比为 0.84（95%CI，0.71 至 1.00；P=0.052）。三组试验中不良事件的发生率相似。