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血嗜酸性粒细胞阈值指导下的重度哮喘患者的抗 IL-5 治疗:间接治疗比较。

Anti-IL-5 treatments in patients with severe asthma by blood eosinophil thresholds: Indirect treatment comparison.

机构信息

Department of Medicine, Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin-Madison, Madison, Wis.

Internal Medicine, Yale University, New Haven, Conn.

出版信息

J Allergy Clin Immunol. 2019 Jan;143(1):190-200.e20. doi: 10.1016/j.jaci.2018.08.031. Epub 2018 Sep 8.

Abstract

BACKGROUND

Three anti-IL-5 pathway-directed therapies are approved for use in patients with severe eosinophilic asthma (SEA); however, no head-to-head comparison data are available.

OBJECTIVE

We sought to compare the efficacy of licensed doses of mepolizumab, benralizumab, and reslizumab in patients with SEA, according to baseline blood eosinophil counts.

METHODS

This indirect treatment comparison (ITC) used data from a Cochrane review and independent searches. Eligible studies were randomized controlled trials in patients aged 12 years or greater with SEA. End points included annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire score and FEV. An ITC was performed in patients with Asthma Control Questionnaire scores of 1.5 or greater and stratified by baseline blood eosinophil count.

RESULTS

Eleven studies were included. All treatments significantly reduced the rate of clinically significant exacerbations and improved asthma control versus placebo in all blood eosinophil count subgroups. Mepolizumab reduced clinically significant exacerbations by 34% to 45% versus benralizumab across subgroups (rate ratio ≥400 cells/μL: 0.55 [95% CI, 0.35-0.87]; ≥300 cells/μL: 0.61 [95% CI, 0.37-0.99]; and ≥150 cells/μL: 0.66 [95% CI, 0.49-0.89]; all P < .05) and by 45% versus reslizumab in the 400 cells/μL or greater subgroup (rate ratio, 0.55 [95% CI, 0.36-0.85]; P = .007). Asthma control was significantly improved with mepolizumab versus benralizumab (all subgroups: P < .05) and versus reslizumab in the 400 cells/μL or greater subgroup (P = .004). Benralizumab significantly improved lung function versus reslizumab in the 400 cells/μL or greater subgroup (P = .025).

CONCLUSIONS

This ITC of the licensed doses suggests that mepolizumab was associated with significantly greater improvements in clinically significant exacerbations and asthma control compared with reslizumab or benralizumab in patients with similar blood eosinophil counts.

摘要

背景

三种抗白细胞介素 5 通路的治疗方法已被批准用于严重嗜酸粒细胞性哮喘(SEA)患者;然而,目前尚无头对头比较数据。

目的

我们旨在根据基线血嗜酸粒细胞计数比较 SEA 患者中许可剂量的美泊利珠单抗、贝那利珠单抗和瑞利珠单抗的疗效。

方法

这项间接治疗比较(ITC)使用了 Cochrane 综述和独立检索的数据。合格的研究为 SEA 患者年龄 12 岁或以上的随机对照试验。终点包括每年临床显著恶化的发生率和哮喘控制问卷评分以及 FEV 的基线变化。在哮喘控制问卷评分≥1.5 的患者中进行了 ITC,并按基线血嗜酸粒细胞计数进行分层。

结果

纳入了 11 项研究。所有治疗均显著降低了临床显著恶化的发生率,并改善了所有血嗜酸粒细胞计数亚组的哮喘控制。美泊利珠单抗降低了临床显著恶化的发生率 34%至 45%,优于贝那利珠单抗在所有亚组(≥400 细胞/μL:比值比 0.55[95%CI,0.35-0.87];≥300 细胞/μL:0.61[95%CI,0.37-0.99];≥150 细胞/μL:0.66[95%CI,0.49-0.89];所有 P<0.05),在≥400 细胞/μL 亚组中优于瑞利珠单抗(比值比 0.55[95%CI,0.36-0.85];P=0.007)。美泊利珠单抗与贝那利珠单抗相比(所有亚组:P<0.05),以及与瑞利珠单抗相比(≥400 细胞/μL 亚组:P=0.004),哮喘控制得到显著改善。贝那利珠单抗在≥400 细胞/μL 亚组中显著改善肺功能,优于瑞利珠单抗(P=0.025)。

结论

这项许可剂量的间接治疗比较表明,与瑞利珠单抗或贝那利珠单抗相比,美泊利珠单抗在基线血嗜酸粒细胞计数相似的患者中,与临床显著恶化和哮喘控制的改善显著相关。

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