阿奇霉素诱导持续性未控制哮喘成年患者哮喘缓解：一项随机、双盲、安慰剂对照试验的二次分析
2024/03/26
摘要
背景：哮喘缓解是一个潜在的治疗目标。
研究问题：与安慰剂相比，在持续未控制的哮喘患者的标准治疗中添加阿奇霉素是否能诱导病情缓解？
研究设计和方法：这项二次分析使用了AMAZES临床试验的数据，这是一项双盲安慰剂对照试验，评估了阿奇霉素治疗哮喘恶化的安全性和有效性。主要缓解定义（称为临床缓解）是在12个月评估时的前6个月内无急性发作和无口服皮质类固醇（OCS），在12个月中哮喘控制问卷（ACQ-5）≤1。二级缓解定义包括临床缓解加肺功能标准（支气管扩张后FEV1≥80%或支气管扩张后FEV1≤5%较基线下降）和完全缓解（痰嗜酸性粒细胞<3%加以上标准）。敏感性分析探讨了原发性和继发性缓解定义的稳健性。确定了临床缓解的预测因素。
结果：335名完成12个月治疗期的参与者（41.5%为男性；中位[Q1，Q3]年龄61.01[51.03，68.73]岁）被纳入分析。在一个亚组患者中，阿奇霉素治疗12个月可诱导哮喘缓解，与安慰剂相比，阿奇霉素组获得临床缓解（50.6%对38.9%；p=0.032）和临床缓解加肺功能标准（50.8%对37.1%；p=0.029）的比例明显更高。此外，阿奇霉素组获得完全缓解的比例更高（23%对13.7%；p=0.058）。敏感性分析支持了这些发现。基线因素，如更好的哮喘相关生活质量和前一年没有OCS爆发，预测了实现临床缓解的几率。阿奇霉素诱导嗜酸性和非嗜酸性哮喘的缓解。
解释：患有持续症状性哮喘的成年人在接受阿奇霉素治疗时获得了更高的缓解率。治疗后的缓解可能是中重度哮喘的一个可实现的治疗目标，未来的研究应将缓解视为一种结果衡量标准。
Dennis Thomas, Vanessa M McDonald, Sean Stevens, Melissa Baraket, Sandra Hodge, Alan James, Christine Jenkins, Guy B Marks, Matthew Peters, Paul Reynolds, John W Upham, Ian A Yang, Peter G Gibson
Abstract
Background: Asthma remission is a potential treatment goal.
Research question: Does adding azithromycin to standard therapy in patients with persistent uncontrolled asthma induce remission compared to placebo?
Study design and methods: This secondary analysis used data from the AMAZES clinical trial - a double-blind placebo-controlled trial that evaluated the safety and efficacy of azithromycin on asthma exacerbations. The primary remission definition (referred to as clinical remission) was zero exacerbations and zero oral corticosteroids (OCS) during the previous six months evaluated at 12 months and Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. Secondary remission definitions included clinical remission plus lung function criteria (post-bronchodilator FEV1≥80% or post-bronchodilator FEV1≤5% decline from baseline) and complete remission (sputum eosinophils<3% plus the above criteria). Sensitivity analyses explored the robustness of primary and secondary remission definitions. The predictors of clinical remission were identified.
Results: 335 participants (41.5% male; median [Q1, Q3] age 61.01 [51.03, 68.73] years) who completed the 12-month treatment period were included in the analysis. Twelve months treatment with azithromycin induced asthma remission in a subgroup of patients, and a significantly higher proportion in the azithromycin arm achieved both clinical remission (50.6% vs 38.9%; p=0.032) and clinical remission plus lung function criteria (50.8% vs 37.1%; p=0.029) compared with placebo. In addition, a higher proportion of the azithromycin group achieved complete remission (23% vs 13.7%; p=0.058). Sensitivity analyses supported these findings. Baseline factors such as better asthma-related quality of life and absence of OCS burst in the previous year predicted the odds of achieving clinical remission. Azithromycin induced remission in both eosinophilic and noneosinophilic asthma.
Interpretation: Adults with persistent symptomatic asthma achieved a higher remission rate when treated with azithromycin. Remission on treatment may be an achievable treatment target in moderate/severe asthma, and future studies should consider remission as an outcome measure.
背景：哮喘缓解是一个潜在的治疗目标。
研究问题：与安慰剂相比，在持续未控制的哮喘患者的标准治疗中添加阿奇霉素是否能诱导病情缓解？
研究设计和方法：这项二次分析使用了AMAZES临床试验的数据，这是一项双盲安慰剂对照试验，评估了阿奇霉素治疗哮喘恶化的安全性和有效性。主要缓解定义（称为临床缓解）是在12个月评估时的前6个月内无急性发作和无口服皮质类固醇（OCS），在12个月中哮喘控制问卷（ACQ-5）≤1。二级缓解定义包括临床缓解加肺功能标准（支气管扩张后FEV1≥80%或支气管扩张后FEV1≤5%较基线下降）和完全缓解（痰嗜酸性粒细胞<3%加以上标准）。敏感性分析探讨了原发性和继发性缓解定义的稳健性。确定了临床缓解的预测因素。
结果：335名完成12个月治疗期的参与者（41.5%为男性；中位[Q1，Q3]年龄61.01[51.03，68.73]岁）被纳入分析。在一个亚组患者中，阿奇霉素治疗12个月可诱导哮喘缓解，与安慰剂相比，阿奇霉素组获得临床缓解（50.6%对38.9%；p=0.032）和临床缓解加肺功能标准（50.8%对37.1%；p=0.029）的比例明显更高。此外，阿奇霉素组获得完全缓解的比例更高（23%对13.7%；p=0.058）。敏感性分析支持了这些发现。基线因素，如更好的哮喘相关生活质量和前一年没有OCS爆发，预测了实现临床缓解的几率。阿奇霉素诱导嗜酸性和非嗜酸性哮喘的缓解。
解释：患有持续症状性哮喘的成年人在接受阿奇霉素治疗时获得了更高的缓解率。治疗后的缓解可能是中重度哮喘的一个可实现的治疗目标，未来的研究应将缓解视为一种结果衡量标准。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Chest. 2024 Feb 29:S0012-3692(24)00284-8. doi: 10.1016/j.chest.2024.02.048.)
Azithromycin induced asthma remission in adults with persistent uncontrolled asthma: a secondary analysis of a randomised, double-blind, placebo-controlled trial(Chest. 2024 Feb 29:S0012-3692(24)00284-8. doi: 10.1016/j.chest.2024.02.048.)
Dennis Thomas, Vanessa M McDonald, Sean Stevens, Melissa Baraket, Sandra Hodge, Alan James, Christine Jenkins, Guy B Marks, Matthew Peters, Paul Reynolds, John W Upham, Ian A Yang, Peter G Gibson
Abstract
Background: Asthma remission is a potential treatment goal.
Research question: Does adding azithromycin to standard therapy in patients with persistent uncontrolled asthma induce remission compared to placebo?
Study design and methods: This secondary analysis used data from the AMAZES clinical trial - a double-blind placebo-controlled trial that evaluated the safety and efficacy of azithromycin on asthma exacerbations. The primary remission definition (referred to as clinical remission) was zero exacerbations and zero oral corticosteroids (OCS) during the previous six months evaluated at 12 months and Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. Secondary remission definitions included clinical remission plus lung function criteria (post-bronchodilator FEV1≥80% or post-bronchodilator FEV1≤5% decline from baseline) and complete remission (sputum eosinophils<3% plus the above criteria). Sensitivity analyses explored the robustness of primary and secondary remission definitions. The predictors of clinical remission were identified.
Results: 335 participants (41.5% male; median [Q1, Q3] age 61.01 [51.03, 68.73] years) who completed the 12-month treatment period were included in the analysis. Twelve months treatment with azithromycin induced asthma remission in a subgroup of patients, and a significantly higher proportion in the azithromycin arm achieved both clinical remission (50.6% vs 38.9%; p=0.032) and clinical remission plus lung function criteria (50.8% vs 37.1%; p=0.029) compared with placebo. In addition, a higher proportion of the azithromycin group achieved complete remission (23% vs 13.7%; p=0.058). Sensitivity analyses supported these findings. Baseline factors such as better asthma-related quality of life and absence of OCS burst in the previous year predicted the odds of achieving clinical remission. Azithromycin induced remission in both eosinophilic and noneosinophilic asthma.
Interpretation: Adults with persistent symptomatic asthma achieved a higher remission rate when treated with azithromycin. Remission on treatment may be an achievable treatment target in moderate/severe asthma, and future studies should consider remission as an outcome measure.
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