美泊利珠单抗减少了重度嗜酸性粒细胞性哮喘患者的恶化，而与体重/体重指数无关：MENSA 和 MUSCA 的荟萃分析。
Mepolizumab reduces exacerbations in patients with severe eosinophilic asthma, irrespective of body weight/body mass index: meta-analysis of MENSA and MUSCA.
机构信息
Respiratory Medical Franchise, GSK, Research Triangle Park, NC, USA.
Present address: Avillion US Inc., Northbrook, IL, USA.
出版信息
Respir Res. 2019 Jul 30;20(1):169. doi: 10.1186/s12931-019-1134-7.
BACKGROUND
We assessed the efficacy of the licensed mepolizumab dose (100 mg subcutaneously [SC]) in patients with severe eosinophilic asthma according to body weight/body mass index (BMI).
METHODS
This was a post hoc individual patient-level meta-analysis of data from the Phase 3 studies MENSA (MEA115588/NCT01691521) and MUSCA (200862/NCT02281318). Patients aged ≥12 years with severe eosinophilic asthma and a history of exacerbations were randomised to 4-weekly placebo, mepolizumab 75 mg intravenously (IV) or 100 mg SC (MENSA) or placebo or mepolizumab 100 mg SC (MUSCA) for 32 (MENSA) or 24 (MUSCA) weeks. The primary endpoint was the annual rate of clinically significant exacerbations; other outcomes included the proportion of patients with no exacerbations, lung function, St George's Respiratory Questionnaire (SGRQ) and Asthma Control Questionnaire-5 (ACQ-5) scores and blood eosinophil counts. Analyses were performed by baseline body weight and BMI (≤60, > 60-75, > 75-90, > 90, < 100, ≥100 kg; ≤25, > 25-30, > 30, < 36, ≥36 kg/m).
RESULTS
Overall, 936 patients received placebo or mepolizumab 100 mg SC. Across all body weight/BMI categories, mepolizumab reduced the rate of clinically significant exacerbations by 49-70% versus placebo. Improvements with mepolizumab versus placebo were also seen in lung function in all body weight/BMI categories except > 90 kg; improvements in SGRQ and ACQ-5 scores were seen across all categories.
CONCLUSIONS
Mepolizumab 100 mg SC has consistent clinical benefits in patients with severe eosinophilic asthma across a range of body weights and BMIs. Data show that the fixed-dose regimen of mepolizumab is suitable, without the need for weight-based dosing.
TRIAL REGISTRATION
This manuscript is a post hoc meta-analysis of data from the Phase 3 studies MENSA and MUSCA. ClinicalTrials.gov, NCT01691521 (MEA115588; MENSA). Registered September 24, 2012. ClinicalTrials.gov, NCT02281318 (200862; MUSCA). Registered November 3, 2014.
背景
我们评估了根据体重/体重指数（BMI）为重度嗜酸性粒细胞性哮喘患者指定的美泊利珠单抗许可剂量（皮下注射 100mg）的疗效。
方法
这是一项事后个体患者水平的荟萃分析，来自 3 期研究 MENSA（MEA115588/NCT01691521）和 MUSCA（200862/NCT02281318）的数据。年龄≥12 岁且有哮喘加重史的重度嗜酸性粒细胞性哮喘患者按 4 周一次的安慰剂、美泊利珠单抗 75mg 静脉注射（IV）或 100mg 皮下注射（MENSA）或安慰剂或美泊利珠单抗 100mg 皮下注射（MUSCA）治疗 32（MENSA）或 24（MUSCA）周。主要终点是临床显著加重的年发生率；其他结果包括无加重的患者比例、肺功能、圣乔治呼吸问卷（SGRQ）和哮喘控制问卷-5（ACQ-5）评分以及血嗜酸性粒细胞计数。分析按基线体重和 BMI（≤60、>60-75、>75-90、>90、<100、≥100kg；≤25、>25-30、>30、<36、≥36kg/m）进行。
结果
总体而言，936 名患者接受了安慰剂或美泊利珠单抗 100mg 皮下注射。在所有体重/BMI 类别中，美泊利珠单抗使临床显著加重的发生率降低了 49%-70%，与安慰剂相比。除了>90kg 以外，在所有体重/BMI 类别中，美泊利珠单抗也改善了肺功能；在所有类别中，SGRQ 和 ACQ-5 评分均有所改善。
结论
在一系列体重和 BMI 范围内，美泊利珠单抗 100mg 皮下注射对重度嗜酸性粒细胞性哮喘患者具有一致的临床获益。数据表明，美泊利珠单抗的固定剂量方案是合适的，无需基于体重进行给药。
试验注册
本文是 3 期研究 MENSA 和 MUSCA 数据的事后荟萃分析。ClinicalTrials.gov，NCT01691521（MEA115588；MENSA）。2012 年 9 月 24 日注册。ClinicalTrials.gov，NCT02281318（200862；MUSCA）。2014 年 11 月 3 日注册。
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