Mepolizumab治疗重症嗜酸性粒细胞性哮喘患者的长期疗效和安全性及其对小气道的影响
2023/08/28
摘要
背景：克利夫兰过敏和哮喘中心的主要问题是需要对重症的嗜酸性粒细胞哮喘患者进行额外的治疗，这些患者是类固醇依赖性的或需要频繁使用泼尼松。
目的：本研究的目的是确定使用ACQ-7、FEV1、FEF25-75%的每月注射mepolizumab 6年半的疗效，以及在超级应答者中的疗效，并了解FEF25-75%是否是评估mepolizumab疗效的有效参数。
方法：我们回顾了67名重症嗜酸性粒细胞性哮喘患者的图表，并比较了47名超级应答者与队列中其他人在ACQ6、ACQ7、嗜酸性粒蛋白、FEV1和FEF25-75%方面的结果。使用中位数和第25和第75个百分位数，就研究终点的初始值和当前值对超级应答者组和所有其他患者进行了描述。研究终点从初始值到当前值的变化是使用百分比变化来测量的。在每组中使用Wilcoxon符号秩检验来检验中值百分比变化为0的零假设。
结果：6年半后，FEV1无明显变化。在超级应答者中，FEF 25-75%的中位百分比显著增加40%（p＜0.001），这显著高于（p＝0.026）在所有其他患者中观察到的13.8%的中位增加百分比。
结论：6年半后使用mepolizumab是安全有效的，与mepolizumab治疗相关的ACQ-7和FEF的显著变化为25-75%，但与FEV1无关。与其他队列相比，在超级应答者中观察到更高程度的变化。在评估重症嗜酸性粒细胞性哮喘对mepolizumab的肺功能反应性方面，FEF 25-75%的变化比FEV1的变化更有意义。
Long-Term Efficacy and Safety Among Patients with Severe Eosinophilic Asthma Treated with Mepolizumab and its Effect on Small Airways
Ronald Strauss, Hannah Leflein, Anna Kolesar, Jeffrey Hammel
Abstract
Background: The major problem at the Cleveland Allergy and Asthma Center was the need for additional therapy for severe eosinophilic asthma patients who were steroid-dependent or requiring frequent bursts of prednisone.
Objectives: The objectives of this study were to determine the efficacy of monthly mepolizumab injections up to 6 ½ years using ACQ-7, FEV1, FEF 25-75% overall and among super-responders, and to understand if FEF 25-75% is an effective parameter to evaluate mepolizumab efficacy.
Methods: We reviewed the charts of 67 patients with severe eosinophilic asthma and compared the results between 47 super-responders and the rest of the cohort regarding ACQ6, ACQ7, eosinophils, FEV1, and FEF 25-75%. The groups of super-responders and all other patients were described with respect to initial and current values of the study endpoints using medians and 25th and 75th percentiles. Changes from the initial to the current values in the study endpoints were measured using percent changes. The Wilcoxon signed rank test was used within each group to test the null hypothesis of 0 median percent change.
Results: After 6 ½ years, there were no significant changes in FEV1. The FEF 25-75%, had a significant median percent increase of 40% among the super-responders (p < 0.001), which was substantially higher (p = 0.026) than the median percent increase of 13.8% observed among all other patients.
Conclusion: The use of mepolizumab after up to 6 ½ years was safe and effective, with significant changes to ACQ-7 and FEF 25-75% associated with mepolizumab treatment, but not the FEV1. A higher magnitude of changes was observed among super-responders when compared to the rest of the cohort. Changes in FEF 25-75% were more meaningful than changes in FEV1 in evaluating pulmonary function responsiveness of severe eosinophilic asthma to mepolizumab.
背景：克利夫兰过敏和哮喘中心的主要问题是需要对重症的嗜酸性粒细胞哮喘患者进行额外的治疗，这些患者是类固醇依赖性的或需要频繁使用泼尼松。
目的：本研究的目的是确定使用ACQ-7、FEV1、FEF25-75%的每月注射mepolizumab 6年半的疗效，以及在超级应答者中的疗效，并了解FEF25-75%是否是评估mepolizumab疗效的有效参数。
方法：我们回顾了67名重症嗜酸性粒细胞性哮喘患者的图表，并比较了47名超级应答者与队列中其他人在ACQ6、ACQ7、嗜酸性粒蛋白、FEV1和FEF25-75%方面的结果。使用中位数和第25和第75个百分位数，就研究终点的初始值和当前值对超级应答者组和所有其他患者进行了描述。研究终点从初始值到当前值的变化是使用百分比变化来测量的。在每组中使用Wilcoxon符号秩检验来检验中值百分比变化为0的零假设。
结果：6年半后，FEV1无明显变化。在超级应答者中，FEF 25-75%的中位百分比显著增加40%（p＜0.001），这显著高于（p＝0.026）在所有其他患者中观察到的13.8%的中位增加百分比。
结论：6年半后使用mepolizumab是安全有效的，与mepolizumab治疗相关的ACQ-7和FEF的显著变化为25-75%，但与FEV1无关。与其他队列相比，在超级应答者中观察到更高程度的变化。在评估重症嗜酸性粒细胞性哮喘对mepolizumab的肺功能反应性方面，FEF 25-75%的变化比FEV1的变化更有意义。
(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)
(J Allergy Clin Immunol Pract. 2023 Aug 10;S2213-2198(23)00910-8. doi: 10.1016/j.jaip.2023.08.010.)
(J Allergy Clin Immunol Pract. 2023 Aug 10;S2213-2198(23)00910-8. doi: 10.1016/j.jaip.2023.08.010.)
Long-Term Efficacy and Safety Among Patients with Severe Eosinophilic Asthma Treated with Mepolizumab and its Effect on Small Airways
Ronald Strauss, Hannah Leflein, Anna Kolesar, Jeffrey Hammel
Abstract
Background: The major problem at the Cleveland Allergy and Asthma Center was the need for additional therapy for severe eosinophilic asthma patients who were steroid-dependent or requiring frequent bursts of prednisone.
Objectives: The objectives of this study were to determine the efficacy of monthly mepolizumab injections up to 6 ½ years using ACQ-7, FEV1, FEF 25-75% overall and among super-responders, and to understand if FEF 25-75% is an effective parameter to evaluate mepolizumab efficacy.
Methods: We reviewed the charts of 67 patients with severe eosinophilic asthma and compared the results between 47 super-responders and the rest of the cohort regarding ACQ6, ACQ7, eosinophils, FEV1, and FEF 25-75%. The groups of super-responders and all other patients were described with respect to initial and current values of the study endpoints using medians and 25th and 75th percentiles. Changes from the initial to the current values in the study endpoints were measured using percent changes. The Wilcoxon signed rank test was used within each group to test the null hypothesis of 0 median percent change.
Results: After 6 ½ years, there were no significant changes in FEV1. The FEF 25-75%, had a significant median percent increase of 40% among the super-responders (p < 0.001), which was substantially higher (p = 0.026) than the median percent increase of 13.8% observed among all other patients.
Conclusion: The use of mepolizumab after up to 6 ½ years was safe and effective, with significant changes to ACQ-7 and FEF 25-75% associated with mepolizumab treatment, but not the FEV1. A higher magnitude of changes was observed among super-responders when compared to the rest of the cohort. Changes in FEF 25-75% were more meaningful than changes in FEV1 in evaluating pulmonary function responsiveness of severe eosinophilic asthma to mepolizumab.
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比较支气管热成形术和生物制剂治疗重度哮喘:系统综述和网络荟萃分析
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Tezepelumab对未控制的严重哮喘的疗效：PATHWAY和NAVIGATOR临床试验的汇总分析
