美泊利单抗治疗重症哮喘的疗效及超级应答者的识别
2020/03/11
摘要
重症哮喘是一种高负担疾病。重度嗜酸性粒细胞哮喘患者应用美泊利单抗的真实世界数据需要用来评估随机对照试验的数据是否适用于更广泛的人群。澳大利亚美泊利单抗登记研究（AMR）建立的目的是评估在澳大利亚美泊利单抗治疗重度嗜酸性粒细胞哮喘的有效性和安全性。有309例重度嗜酸性粒细胞哮喘（中位年龄60岁，58%女性）患者使用美泊利单抗。这些患者症状控制差[哮喘控制问卷（ACQ）-5中位分数为3.4]，加重频繁[过去12个月口服皮质类固醇（OCS）的中位次数3次]，47%需要每日应用OCS。中位基线外周血嗜酸性粒细胞水平为590个/µL。合并症常见：变应性鼻炎63%，胃食管反流病52%，肥胖46%，鼻息肉34%。美泊利单抗治疗后与一年相比，需OCS的加重（年化率比0.34[95%可信区间0.29-0.41]，p<0.001）和住院率（比率0.46[95%CI 0.33-0.63]，p<0.001）下降。治疗改善了症状控制（6个月时 ACQ-5平均降低2.0）、生活质量和肺功能。较高的血嗜酸性粒细胞水平（p=0.003）和较晚的哮喘发病年龄（p=0.028）预示着对美泊利单抗有较好的反应，而男性（p=0.031）或体质指数≥30（p=0.043）则预示着较低的反应。超级应答者（ACQ-5升高25%以上的应答者，n=61，24%）有较高的T2疾病负担和较少的合并症。美泊利单抗治疗有效地降低了真实世界中重度嗜酸性粒细胞哮喘患者显著及长期的疾病负担。
Mepolizumab effectiveness and identification of super-responders in severe asthma.
Harvey ES, Langton D, Katelaris C, Stevens S, Farah CS, Gillman A, Harrington J, Hew M, Kritikos V, Radhakrishna N, Bardin P, Peters M, Reynolds PN, Upham JW, Baraket M, Bowler S, Bowden J, Chien J, Chung LP, Grainge C, Jenkins C, Katsoulotos GP, Lee J, McDonald VM, Reddel HK, Rimmer J, Wark PAB, Gibson PG.
Abstract
Severe asthma is a high burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control [median AsthmaControl Questionnaire (ACQ)-5 score of 3.4], frequent exacerbations [median 3 courses of oral corticosteroids (OCS) in the previous 12 months], and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL-1 Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared to the previous year (annualised rate ratio 0.34 [95% CI 0.29-0.41], p<0.001) and hospitalisations (rate ratio 0.46 [95% CI 0.33-0.63], p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.
重症哮喘是一种高负担疾病。重度嗜酸性粒细胞哮喘患者应用美泊利单抗的真实世界数据需要用来评估随机对照试验的数据是否适用于更广泛的人群。澳大利亚美泊利单抗登记研究（AMR）建立的目的是评估在澳大利亚美泊利单抗治疗重度嗜酸性粒细胞哮喘的有效性和安全性。有309例重度嗜酸性粒细胞哮喘（中位年龄60岁，58%女性）患者使用美泊利单抗。这些患者症状控制差[哮喘控制问卷（ACQ）-5中位分数为3.4]，加重频繁[过去12个月口服皮质类固醇（OCS）的中位次数3次]，47%需要每日应用OCS。中位基线外周血嗜酸性粒细胞水平为590个/µL。合并症常见：变应性鼻炎63%，胃食管反流病52%，肥胖46%，鼻息肉34%。美泊利单抗治疗后与一年相比，需OCS的加重（年化率比0.34[95%可信区间0.29-0.41]，p<0.001）和住院率（比率0.46[95%CI 0.33-0.63]，p<0.001）下降。治疗改善了症状控制（6个月时 ACQ-5平均降低2.0）、生活质量和肺功能。较高的血嗜酸性粒细胞水平（p=0.003）和较晚的哮喘发病年龄（p=0.028）预示着对美泊利单抗有较好的反应，而男性（p=0.031）或体质指数≥30（p=0.043）则预示着较低的反应。超级应答者（ACQ-5升高25%以上的应答者，n=61，24%）有较高的T2疾病负担和较少的合并症。美泊利单抗治疗有效地降低了真实世界中重度嗜酸性粒细胞哮喘患者显著及长期的疾病负担。
(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)
(Eur Respir J. 2020 Mar 5. pii: 1902420. doi: 10.1183/13993003.02420-2019.)
(Eur Respir J. 2020 Mar 5. pii: 1902420. doi: 10.1183/13993003.02420-2019.)
Mepolizumab effectiveness and identification of super-responders in severe asthma.
Harvey ES, Langton D, Katelaris C, Stevens S, Farah CS, Gillman A, Harrington J, Hew M, Kritikos V, Radhakrishna N, Bardin P, Peters M, Reynolds PN, Upham JW, Baraket M, Bowler S, Bowden J, Chien J, Chung LP, Grainge C, Jenkins C, Katsoulotos GP, Lee J, McDonald VM, Reddel HK, Rimmer J, Wark PAB, Gibson PG.
Abstract
Severe asthma is a high burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control [median AsthmaControl Questionnaire (ACQ)-5 score of 3.4], frequent exacerbations [median 3 courses of oral corticosteroids (OCS) in the previous 12 months], and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL-1 Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared to the previous year (annualised rate ratio 0.34 [95% CI 0.29-0.41], p<0.001) and hospitalisations (rate ratio 0.46 [95% CI 0.33-0.63], p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.
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固定剂量皮下注射reslizumab对重度非控制性哮喘患者哮喘急性发作和口服激素依赖性哮喘患者皮质类固醇剂量的影响：来自
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生物学与疗法的交叉点：成人哮喘的2型靶向疗法
