美伯利单抗在重症难控制嗜酸性粒细胞性哮喘中替代奥玛珠单抗的临床益处
2019/05/10
摘要
背景：美伯利单抗和奥玛珠单抗用于治疗不同但有重叠的重症哮喘表型
目标：为了评估能够应用两种生物制剂但只应用奥玛珠单抗未达到最佳控制水平的患者在直接转换为应用美伯利单抗后能否改善哮喘控制。
方法：OSMO是一项多中心、开放式、单组、为期32周的临床试验，入组患者为目前应用大剂量激素、其他控制药物及应用奥玛珠单抗≥4个月并且入组前一年≥2次哮喘急性发作的患者。基线水平时，外周血嗜酸性粒细胞≥150细胞/μL（或过去一年≥300细胞/μL）及ACQ评分≥1.5的患者停用奥玛珠单抗并立即开始每4周皮下注射美伯利单抗100 mg。终点指标包括ACQ-5评分、SGRQ评分以及治疗反应者ACQ-5、SGRQ评分的变化比例、试验期间的年恶化比率。
结果：在第32周（有意向治疗人群[n = 145]），ACQ-5和SGRQ总分的最小二乘（LS）均值变化（标准误差[SE]）分别为-1.45（0.107）和-19.0（1.64）分; 77％和79％的患者分别达到最小临床重要差异（ACQ-5：≥0.5分; SGRQ：≥4分）。临床恶化年率为1.18次/年，比去年的3.26次/年下降64％。安全性和免疫原性与既往试验一致。
结论：在从奥玛珠单抗直接转换为应用美伯利单抗后，重症难控制嗜酸性粒细胞性哮喘患者在哮喘控制水平、健康状况及恶化率方面临床上显着改善，并且无耐受性问题报道出现。
The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma.
Chapman KR, Albers FC, Chipps B, Muñoz X, Devouassoux G, Bergna M, Galkin D, Azmi J, Mouneimne D, Price RG, Liu MC.
Abstract
BACKGROUND:Mepolizumab and omalizumab are treatments for distinct but overlapping severe
asthma phenotypes.
OBJECTIVE:To assess if patients eligible for both biologics but not optimally controlled with omalizumab experience improved asthma control when switched directly to mepolizumab.
METHODS:OSMO was a multicenter, open-label, single-arm, 32-week trial in patients with ≥2 asthma exacerbations in the year prior to enrollment, despite receiving high-dose inhaled corticosteroids and other controller(s), plus omalizumab (≥4 months). At baseline, patients with blood eosinophil counts ≥150 cells/μL (or ≥300 cells/μL in the prior year) and an Asthma Control Questionnaire (ACQ)-5 score ≥1.5 discontinued omalizumab and immediately commenced mepolizumab 100 mg subcutaneously every 4 weeks. Endpoints included change from baseline in ACQ-5 score (primary), St George's Respiratory Questionnaire (SGRQ) score and the proportions of ACQ-5 and SGRQ responders, all at Week 32, and the annualized exacerbation rate over the study period.
RESULTS:At Week 32 (intent-to-treat population [n=145]), the least squares (LS) mean changes (standard error [SE]) in ACQ-5 and SGRQ total scores were -1.45 (0.107) and -19.0 (1.64) points; with 77% and 79% of patients achieving the minimum clinically important differences (ACQ-5: ≥0.5 points; SGRQ: ≥4 points), respectively. The annualized rate of clinically significant exacerbations was 1.18 events/year, a 64% reduction from 3.26 events/year during the previous year. Safety and immunogenicity profiles were consistent with previous trials.
CONCLUSION:After directly switching from omalizumab to mepolizumab, patients with uncontrolled severe eosinophilic asthma experienced clinically significant improvements in asthma control, health status and exacerbation rate, with no tolerability issues reported.
背景：美伯利单抗和奥玛珠单抗用于治疗不同但有重叠的重症哮喘表型
目标：为了评估能够应用两种生物制剂但只应用奥玛珠单抗未达到最佳控制水平的患者在直接转换为应用美伯利单抗后能否改善哮喘控制。
方法：OSMO是一项多中心、开放式、单组、为期32周的临床试验，入组患者为目前应用大剂量激素、其他控制药物及应用奥玛珠单抗≥4个月并且入组前一年≥2次哮喘急性发作的患者。基线水平时，外周血嗜酸性粒细胞≥150细胞/μL（或过去一年≥300细胞/μL）及ACQ评分≥1.5的患者停用奥玛珠单抗并立即开始每4周皮下注射美伯利单抗100 mg。终点指标包括ACQ-5评分、SGRQ评分以及治疗反应者ACQ-5、SGRQ评分的变化比例、试验期间的年恶化比率。
结果：在第32周（有意向治疗人群[n = 145]），ACQ-5和SGRQ总分的最小二乘（LS）均值变化（标准误差[SE]）分别为-1.45（0.107）和-19.0（1.64）分; 77％和79％的患者分别达到最小临床重要差异（ACQ-5：≥0.5分; SGRQ：≥4分）。临床恶化年率为1.18次/年，比去年的3.26次/年下降64％。安全性和免疫原性与既往试验一致。
结论：在从奥玛珠单抗直接转换为应用美伯利单抗后，重症难控制嗜酸性粒细胞性哮喘患者在哮喘控制水平、健康状况及恶化率方面临床上显着改善，并且无耐受性问题报道出现。
（中日友好医院呼吸与危重症医学科 张鑫 摘译 林江涛 审校）
（Allergy. 2019 May 2. doi: 10.1111/all.13850）
（Allergy. 2019 May 2. doi: 10.1111/all.13850）
The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma.
Chapman KR, Albers FC, Chipps B, Muñoz X, Devouassoux G, Bergna M, Galkin D, Azmi J, Mouneimne D, Price RG, Liu MC.
Abstract
BACKGROUND:Mepolizumab and omalizumab are treatments for distinct but overlapping severe
asthma phenotypes.
OBJECTIVE:To assess if patients eligible for both biologics but not optimally controlled with omalizumab experience improved asthma control when switched directly to mepolizumab.
METHODS:OSMO was a multicenter, open-label, single-arm, 32-week trial in patients with ≥2 asthma exacerbations in the year prior to enrollment, despite receiving high-dose inhaled corticosteroids and other controller(s), plus omalizumab (≥4 months). At baseline, patients with blood eosinophil counts ≥150 cells/μL (or ≥300 cells/μL in the prior year) and an Asthma Control Questionnaire (ACQ)-5 score ≥1.5 discontinued omalizumab and immediately commenced mepolizumab 100 mg subcutaneously every 4 weeks. Endpoints included change from baseline in ACQ-5 score (primary), St George's Respiratory Questionnaire (SGRQ) score and the proportions of ACQ-5 and SGRQ responders, all at Week 32, and the annualized exacerbation rate over the study period.
RESULTS:At Week 32 (intent-to-treat population [n=145]), the least squares (LS) mean changes (standard error [SE]) in ACQ-5 and SGRQ total scores were -1.45 (0.107) and -19.0 (1.64) points; with 77% and 79% of patients achieving the minimum clinically important differences (ACQ-5: ≥0.5 points; SGRQ: ≥4 points), respectively. The annualized rate of clinically significant exacerbations was 1.18 events/year, a 64% reduction from 3.26 events/year during the previous year. Safety and immunogenicity profiles were consistent with previous trials.
CONCLUSION:After directly switching from omalizumab to mepolizumab, patients with uncontrolled severe eosinophilic asthma experienced clinically significant improvements in asthma control, health status and exacerbation rate, with no tolerability issues reported.
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莫米松或噻托溴铵与痰低嗜酸性粒细胞水平轻度哮喘治疗
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