Benralizumab能减少重症哮喘患者口服糖皮质激素
2017/10/09
摘要
背景：许多重症哮喘患者的治疗都依赖于口服糖皮质激素。Benralizumab是一种靶向于白介素-5受体α亚单位的单克隆抗体，它能显著降低哮喘急性发作的发生率。我们以需依赖于口服糖皮质激素治疗的重症嗜酸性粒细胞性哮喘患者为研究对象，探讨benralizumab是否可以有效减少这些患者口服糖皮质激素剂量。
方法：在这项为期28周的随机对照试验中，在保持成年重度哮喘患者是处于哮喘控制的情况下，试验组患者予以皮下注射benralizumab（每次30mg，每4周注射一次或者每次30mg，前3次剂量每4周注射一次，以后每8周注射一次），对照组患者予以安慰剂治疗，评估benralizumab在减少患者口服糖皮质激素剂量方面的效应。以28周时患者口服糖皮质激素剂量相对于基线改变的百分比为主要终点，并评估研究对象的每年哮喘加重率、肺功能、症状和安全性。
结果：369位病人入选，共220位随机化并接受了benralizumab或安慰剂治疗。相对于安慰剂组，治疗组患者口服糖皮质激素量减少了25%，两种benralizumab给药方案所在的试验组，其中位口服糖皮质激素量相对于基线减少了75%（两组间比P<0.001）。benralizumab组口服糖皮质激素减少的患者比例约超过了安慰剂组的4倍。在次要终点中，每4周benralizumab注射组中患者的每年加重率要比安慰剂组低55%(边缘率,0.83 vs. 1.83, P=0.003)；每8周benralizumab注射组中患者的每年加重率要比安慰剂组低70%(边缘率, 0.54 vs. 1.83, P<0.001)。在28周时，相对于安慰剂组，两种benralizumab给药组均对患者的第1秒用力呼气容积(FEV1)无显著影响。Benralizumab在多项哮喘症状指标中的效应不一，一些显示出显著的变化，而另一些则没有显著的变化。不良反应的发生率在benralizumab给药组和安慰剂组中大致相当。
结论：与安慰剂相比较，Benralizumab在口服糖皮质激素和哮喘加重率等方面展示出了明显的临床相关利益。但这些作用并不会对FEV1产生持续性的效应。
Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma.
Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M; ZONDA Trial Investigators.
Collaborators (58)
Abstract
BACKGROUND:Many patients with severe asthma rely on oral glucocorticoids to manage their disease. We investigated whether benralizumab, a monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor that significantly reduces the incidence of asthma exacerbations, was also effective as an oral glucocorticoid-sparing therapy in patients relying on oral glucocorticoids to manage severe asthma associated with eosinophilia.
METHODS:In a 28-week randomized, controlled trial, we assessed the effects of benralizumab (at a dose of 30 mg administered subcutaneously either every 4 weeks or every 8 weeks [with the first three doses administered every 4 weeks]) versus placebo on the reduction in the oral glucocorticoid dose while asthma control was maintained in adult patients with severe asthma. The primary end point was the percentage change in the oral glucocorticoid dose from baseline to week 28. Annual asthma exacerbation rates, lung function, symptoms, and safety were assessed.
RESULTS:Of 369 patients enrolled, 220 underwent randomization and started receiving benralizumab or placebo. The two benralizumab dosing regimens significantly reduced the median final oral glucocorticoid doses from baseline by 75%, as compared with a reduction of 25% in the oral glucocorticoid doses in the placebo group (P<0.001 for both comparisons). The odds of a reduction in the oral glucocorticoid dose were more than 4 times as high with benralizumab as with placebo. Among the secondary outcomes, benralizumab administered every 4 weeks resulted in an annual exacerbation rate that was 55% lower than the rate with placebo (marginal rate, 0.83 vs. 1.83, P=0.003), and benralizumab administered every 8 weeks resulted in an annual exacerbation rate that was 70% lower than the rate with placebo (marginal rate, 0.54 vs. 1.83, P<0.001). At 28 weeks, there was no significant effect of either benralizumab regimen on the forced expiratory volume in 1 second (FEV1), as compared with placebo. The effects on various measures of asthma symptoms were mixed, with some showing significant changes in favor of benralizumab and others not showing significant changes. Frequencies of adverse events were similar between each benralizumab group and the placebo group.
CONCLUSIONS:Benralizumab showed significant, clinically relevant benefits, as compared with placebo, on oral glucocorticoid use and exacerbation rates. These effects occurred without a sustained effect on the FEV1. (Funded by AstraZeneca; ZONDA ClinicalTrials.gov number, NCT02075255 .).
背景：许多重症哮喘患者的治疗都依赖于口服糖皮质激素。Benralizumab是一种靶向于白介素-5受体α亚单位的单克隆抗体，它能显著降低哮喘急性发作的发生率。我们以需依赖于口服糖皮质激素治疗的重症嗜酸性粒细胞性哮喘患者为研究对象，探讨benralizumab是否可以有效减少这些患者口服糖皮质激素剂量。
方法：在这项为期28周的随机对照试验中，在保持成年重度哮喘患者是处于哮喘控制的情况下，试验组患者予以皮下注射benralizumab（每次30mg，每4周注射一次或者每次30mg，前3次剂量每4周注射一次，以后每8周注射一次），对照组患者予以安慰剂治疗，评估benralizumab在减少患者口服糖皮质激素剂量方面的效应。以28周时患者口服糖皮质激素剂量相对于基线改变的百分比为主要终点，并评估研究对象的每年哮喘加重率、肺功能、症状和安全性。
结果：369位病人入选，共220位随机化并接受了benralizumab或安慰剂治疗。相对于安慰剂组，治疗组患者口服糖皮质激素量减少了25%，两种benralizumab给药方案所在的试验组，其中位口服糖皮质激素量相对于基线减少了75%（两组间比P<0.001）。benralizumab组口服糖皮质激素减少的患者比例约超过了安慰剂组的4倍。在次要终点中，每4周benralizumab注射组中患者的每年加重率要比安慰剂组低55%(边缘率,0.83 vs. 1.83, P=0.003)；每8周benralizumab注射组中患者的每年加重率要比安慰剂组低70%(边缘率, 0.54 vs. 1.83, P<0.001)。在28周时，相对于安慰剂组，两种benralizumab给药组均对患者的第1秒用力呼气容积(FEV1)无显著影响。Benralizumab在多项哮喘症状指标中的效应不一，一些显示出显著的变化，而另一些则没有显著的变化。不良反应的发生率在benralizumab给药组和安慰剂组中大致相当。
结论：与安慰剂相比较，Benralizumab在口服糖皮质激素和哮喘加重率等方面展示出了明显的临床相关利益。但这些作用并不会对FEV1产生持续性的效应。
（复旦大学附属中山医院呼吸内科 胡湘麟 摘译 杨冬 审校）
（N Engl J Med. 2017 Jun 22;376(25):2448-2458.）
（N Engl J Med. 2017 Jun 22;376(25):2448-2458.）
Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma.
Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M; ZONDA Trial Investigators.
Collaborators (58)
Abstract
BACKGROUND:Many patients with severe asthma rely on oral glucocorticoids to manage their disease. We investigated whether benralizumab, a monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor that significantly reduces the incidence of asthma exacerbations, was also effective as an oral glucocorticoid-sparing therapy in patients relying on oral glucocorticoids to manage severe asthma associated with eosinophilia.
METHODS:In a 28-week randomized, controlled trial, we assessed the effects of benralizumab (at a dose of 30 mg administered subcutaneously either every 4 weeks or every 8 weeks [with the first three doses administered every 4 weeks]) versus placebo on the reduction in the oral glucocorticoid dose while asthma control was maintained in adult patients with severe asthma. The primary end point was the percentage change in the oral glucocorticoid dose from baseline to week 28. Annual asthma exacerbation rates, lung function, symptoms, and safety were assessed.
RESULTS:Of 369 patients enrolled, 220 underwent randomization and started receiving benralizumab or placebo. The two benralizumab dosing regimens significantly reduced the median final oral glucocorticoid doses from baseline by 75%, as compared with a reduction of 25% in the oral glucocorticoid doses in the placebo group (P<0.001 for both comparisons). The odds of a reduction in the oral glucocorticoid dose were more than 4 times as high with benralizumab as with placebo. Among the secondary outcomes, benralizumab administered every 4 weeks resulted in an annual exacerbation rate that was 55% lower than the rate with placebo (marginal rate, 0.83 vs. 1.83, P=0.003), and benralizumab administered every 8 weeks resulted in an annual exacerbation rate that was 70% lower than the rate with placebo (marginal rate, 0.54 vs. 1.83, P<0.001). At 28 weeks, there was no significant effect of either benralizumab regimen on the forced expiratory volume in 1 second (FEV1), as compared with placebo. The effects on various measures of asthma symptoms were mixed, with some showing significant changes in favor of benralizumab and others not showing significant changes. Frequencies of adverse events were similar between each benralizumab group and the placebo group.
CONCLUSIONS:Benralizumab showed significant, clinically relevant benefits, as compared with placebo, on oral glucocorticoid use and exacerbation rates. These effects occurred without a sustained effect on the FEV1. (Funded by AstraZeneca; ZONDA ClinicalTrials.gov number, NCT02075255 .).
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对重度嗜酸性粒细胞性哮喘患者使用mepolizumab：III期MENSA试验的经济学分析
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重症哮喘患者Benralizumab增强反应的预测因素：SIROCCO和CALIMA研究的汇总分析
