地塞米松治疗嗜酸性哮喘（EXHALE）的安全性和有效性：一项随机对照试验
2023/07/21
摘要
背景：需要新的、有效的口服哮喘疗法。地塞米松，一种口服的降低嗜酸性粒细胞的药物，以前没有在哮喘中进行过研究。
目的：我们试图评估地塞米松降低嗜酸性哮喘患者血液和气道嗜酸性粒细胞的安全性和有效性。
方法：我们对患有中度至重度哮喘且血液绝对嗜酸性粒细胞计数（AEC）大于或等于300/μL的成人进行了一项随机、双盲、安慰剂对照的概念验证试验。受试者被随机分配（1:1:1:1）给地塞米松37.5、75或150 mg BID（每日两次）或安慰剂。主要终点是从基线到第12周AEC的相对变化。支气管扩张剂前FEV1第12周与基线相比的变化是一个关键的次要终点。鼻嗜酸性粒细胞过氧化物酶是一个探索性终点。
结果：共有103名受试者被随机分为地塞米松37.5 mg BID（N=22）、75 mg BID、150 mg BID或安慰剂（N=27）。在150 mg BID（OR，0.23；95%CI，0.12-0.43；P<.0001）和75 mg BID剂量组（OR，0.34；95%CI，0.18-0.65；P=.0014）中，地塞米松显著降低了安慰剂校正的AEC第12周与基线的比值，分别降低了77%和66%。在150 mg BID（中位数，0.11；P=0.020）组和75 mg BID组（中位数，0.17；P=0.021）中，地塞米松使鼻嗜酸性粒细胞过氧化物酶第12周比率的探索终点降低至基线。从第4周开始观察到安慰剂校正的FEV1增加（无显著性）。地塞米松显示出良好的安全性。
结论：地塞米松能有效降低嗜酸性粒细胞，耐受性良好。需要更多更大规模的临床试验来了解地塞米松治疗哮喘的临床疗效。
Safety and Efficacy of Dexpramipexole in Eosinophilic Asthma (EXHALE): A randomized controlled trial
Salman Siddiqui, Sally E Wenzel, Michael E Bozik, Donald G Archibald, Steven I Dworetzky, James L Mather, Randall Killingsworth, Natasha Ghearing, Justin T Schwartz, Sergei I Ochkur, Elizabeth A Jacobsen, William W Busse, Reynold A Panettieri, Calman Prussin
Abstract
Background: There is a need for new and effective oral asthma therapies. Dexpramipexole, an oral eosinophil-lowering drug, has not previously been studied in asthma.
Objective: We sought to evaluate the safety and efficacy of dexpramipexole in lowering blood and airway eosinophilia in subjects with eosinophilic asthma.
Methods: We performed a randomized, double-blind, placebo-controlled proof-of-concept trial in adults with inadequately controlled moderate to severe asthma and blood absolute eosinophil count (AEC) greater than or equal to 300/μL. Subjects were randomly assigned (1:1:1:1) to dexpramipexole 37.5, 75, or 150 mg BID (twice-daily) or placebo. The primary end point was the relative change in AEC from baseline to week 12. Prebronchodilator FEV1 week-12 change from baseline was a key secondary end point. Nasal eosinophil peroxidase was an exploratory end point.
Results: A total of 103 subjects were randomly assigned to dexpramipexole 37.5 mg BID (N = 22), 75 mg BID (N = 26), 150 mg BID (N = 28), or placebo (N = 27). Dexpramipexole significantly reduced placebo-corrected AEC week-12 ratio to baseline, in both the 150-mg BID (ratio, 0.23; 95% CI, 0.12-0.43; P < .0001) and the 75-mg BID (ratio, 0.34; 95% CI, 0.18-0.65; P = .0014) dose groups, corresponding to 77% and 66% reductions, respectively. Dexpramipexole reduced the exploratory end point of nasal eosinophil peroxidase week-12 ratio to baseline in the 150-mg BID (median, 0.11; P = .020) and the 75-mg BID (median, 0.17; P = .021) groups. Placebo-corrected FEV1 increases were observed starting at week 4 (nonsignificant). Dexpramipexole displayed a favorable safety profile.
Conclusions: Dexpramipexole demonstrated effective eosinophil lowering and was well tolerated. Additional larger clinical trials are needed to understand the clinical efficacy of dexpramipexole in asthma.
背景：需要新的、有效的口服哮喘疗法。地塞米松，一种口服的降低嗜酸性粒细胞的药物，以前没有在哮喘中进行过研究。
目的：我们试图评估地塞米松降低嗜酸性哮喘患者血液和气道嗜酸性粒细胞的安全性和有效性。
方法：我们对患有中度至重度哮喘且血液绝对嗜酸性粒细胞计数（AEC）大于或等于300/μL的成人进行了一项随机、双盲、安慰剂对照的概念验证试验。受试者被随机分配（1:1:1:1）给地塞米松37.5、75或150 mg BID（每日两次）或安慰剂。主要终点是从基线到第12周AEC的相对变化。支气管扩张剂前FEV1第12周与基线相比的变化是一个关键的次要终点。鼻嗜酸性粒细胞过氧化物酶是一个探索性终点。
结果：共有103名受试者被随机分为地塞米松37.5 mg BID（N=22）、75 mg BID、150 mg BID或安慰剂（N=27）。在150 mg BID（OR，0.23；95%CI，0.12-0.43；P<.0001）和75 mg BID剂量组（OR，0.34；95%CI，0.18-0.65；P=.0014）中，地塞米松显著降低了安慰剂校正的AEC第12周与基线的比值，分别降低了77%和66%。在150 mg BID（中位数，0.11；P=0.020）组和75 mg BID组（中位数，0.17；P=0.021）中，地塞米松使鼻嗜酸性粒细胞过氧化物酶第12周比率的探索终点降低至基线。从第4周开始观察到安慰剂校正的FEV1增加（无显著性）。地塞米松显示出良好的安全性。
结论：地塞米松能有效降低嗜酸性粒细胞，耐受性良好。需要更多更大规模的临床试验来了解地塞米松治疗哮喘的临床疗效。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2023 Jun 3;S0091-6749(23)00709-1. doi: 10.1016/j.jaci.2023.05.014. Online ahead of print.)
(J Allergy Clin Immunol. 2023 Jun 3;S0091-6749(23)00709-1. doi: 10.1016/j.jaci.2023.05.014. Online ahead of print.)
Safety and Efficacy of Dexpramipexole in Eosinophilic Asthma (EXHALE): A randomized controlled trial
Salman Siddiqui, Sally E Wenzel, Michael E Bozik, Donald G Archibald, Steven I Dworetzky, James L Mather, Randall Killingsworth, Natasha Ghearing, Justin T Schwartz, Sergei I Ochkur, Elizabeth A Jacobsen, William W Busse, Reynold A Panettieri, Calman Prussin
Abstract
Background: There is a need for new and effective oral asthma therapies. Dexpramipexole, an oral eosinophil-lowering drug, has not previously been studied in asthma.
Objective: We sought to evaluate the safety and efficacy of dexpramipexole in lowering blood and airway eosinophilia in subjects with eosinophilic asthma.
Methods: We performed a randomized, double-blind, placebo-controlled proof-of-concept trial in adults with inadequately controlled moderate to severe asthma and blood absolute eosinophil count (AEC) greater than or equal to 300/μL. Subjects were randomly assigned (1:1:1:1) to dexpramipexole 37.5, 75, or 150 mg BID (twice-daily) or placebo. The primary end point was the relative change in AEC from baseline to week 12. Prebronchodilator FEV1 week-12 change from baseline was a key secondary end point. Nasal eosinophil peroxidase was an exploratory end point.
Results: A total of 103 subjects were randomly assigned to dexpramipexole 37.5 mg BID (N = 22), 75 mg BID (N = 26), 150 mg BID (N = 28), or placebo (N = 27). Dexpramipexole significantly reduced placebo-corrected AEC week-12 ratio to baseline, in both the 150-mg BID (ratio, 0.23; 95% CI, 0.12-0.43; P < .0001) and the 75-mg BID (ratio, 0.34; 95% CI, 0.18-0.65; P = .0014) dose groups, corresponding to 77% and 66% reductions, respectively. Dexpramipexole reduced the exploratory end point of nasal eosinophil peroxidase week-12 ratio to baseline in the 150-mg BID (median, 0.11; P = .020) and the 75-mg BID (median, 0.17; P = .021) groups. Placebo-corrected FEV1 increases were observed starting at week 4 (nonsignificant). Dexpramipexole displayed a favorable safety profile.
Conclusions: Dexpramipexole demonstrated effective eosinophil lowering and was well tolerated. Additional larger clinical trials are needed to understand the clinical efficacy of dexpramipexole in asthma.
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过敏性鼻炎和哮喘控制与EQ-5D-5L结构域损害：一项MASK-air真实世界研究
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高强度间歇训练对哮喘患者吸入糖皮质激素剂量的影响：一项随机对照试验
