Benralizumab治疗过敏性哮喘：随机、双盲、安慰剂对照试验
2024/09/29
摘要
背景：Benralizumab可诱导血液和肺组织中的嗜酸性粒细胞快速、近乎完全地耗竭。我们研究了Benralizumab能否减轻过敏性哮喘患者由过敏原诱发的迟发性哮喘反应（LAR）。
方法：筛选出痰中嗜酸性粒细胞和 LAR 增高的过敏性哮喘患者，随机给予Benralizumab 30 毫克或匹配的安慰剂，每 4 周一次，共 8 周（3 次）。在第 9 周和第 12 周进行过敏原激发，评估血液、痰液、骨髓和支气管组织中的嗜酸性粒细胞和 LAR。
结果：46 名参与者（平均年龄 30.9 岁）被随机分配到Benralizumab组（23 人）或安慰剂组（23 人）。与安慰剂相比，benralizumab 组的嗜酸性粒细胞在治疗开始后 4 周的血液及 治疗开始后9周的痰液和骨髓中明显减少。在第9周过敏原激发后7小时，与安慰剂相比，Benralizumab组的痰嗜酸性粒细胞显著减弱（最小二乘均值差异-5.81%，95% CI -10.69--0.94%；p=0.021）；然而，LAR没有明显差异（最小二乘均值差异2.54%，95% CI 3.05-8.12%；p=0.363）。Benralizumab组和安慰剂组分别有 7 人（30.4%）和 14 人（60.9%）出现不良事件。
结论：Benralizumab 给药 8 周后，轻度过敏性哮喘患者血液、骨髓和痰中的嗜酸性粒细胞显著减少；但是，LAR 没有变化，这表明嗜酸性粒细胞本身并不是过敏原诱发支气管收缩的关键因素。
Benralizumab for allergic asthma: a randomised, double-blind, placebo-controlled trial
Gauvreau GM, Sehmi R, FitzGerald JM, Leigh R, Cockcroft DW, Davis BE, Mayers I, Boulet LP, Al-Sajee D, Salter BM, Cusack RP, Ho T, Whetstone CE, Alsaji N, Satia I, Killian KJ, Mitchell PD, Magee IP, Bergeron C, Bhutani M, Werkström V, Durżyński T, Shoemaker K, Katial RK, Jison M, Newbold P, McCrae C, O'Byrne PM.
Abstract
Background:Benralizumab induces rapid and near-complete depletion of eosinophils from blood and lung tissue. We investigated whether benralizumab could attenuate the allergen-induced late asthmatic response (LAR) in participants with allergic asthma.
Methods:Participants with allergic asthma who demonstrated increased sputum eosinophils and LAR at screening were randomised to benralizumab 30 mg or matched placebo given every 4 weeks for 8 weeks (3 doses). Allergen challenges were performed at weeks 9 and 12 when blood, sputum, bone marrow and bronchial tissue eosinophils and LAR were assessed.
Results:46 participants (mean age 30.9 years) were randomised to benralizumab (n=23) or placebo (n=23). Eosinophils were significantly reduced in the benralizumab group compared with placebo in blood at 4 weeks and sputum and bone marrow at 9 weeks after treatment initiation. At 7 h after an allergen challenge at week 9, sputum eosinophilia was significantly attenuated in the benralizumab group compared to placebo (least squares mean difference -5.81%, 95% CI -10.69- -0.94%; p=0.021); however, the LAR was not significantly different (least squares mean difference 2.54%, 95% CI 3.05-8.12%; p=0.363). Adverse events were reported for seven (30.4%) and 14 (60.9%) participants in the benralizumab and placebo groups, respectively.
Conclusion:Benralizumab administration over 8 weeks resulted in a significant attenuation of blood, bone marrow and sputum eosinophilia in participants with mild allergic asthma; however, there was no change in the LAR, suggesting that eosinophils alone are not a key component of allergen-induced bronchoconstriction.
背景：Benralizumab可诱导血液和肺组织中的嗜酸性粒细胞快速、近乎完全地耗竭。我们研究了Benralizumab能否减轻过敏性哮喘患者由过敏原诱发的迟发性哮喘反应（LAR）。
方法：筛选出痰中嗜酸性粒细胞和 LAR 增高的过敏性哮喘患者，随机给予Benralizumab 30 毫克或匹配的安慰剂，每 4 周一次，共 8 周（3 次）。在第 9 周和第 12 周进行过敏原激发，评估血液、痰液、骨髓和支气管组织中的嗜酸性粒细胞和 LAR。
结果：46 名参与者（平均年龄 30.9 岁）被随机分配到Benralizumab组（23 人）或安慰剂组（23 人）。与安慰剂相比，benralizumab 组的嗜酸性粒细胞在治疗开始后 4 周的血液及 治疗开始后9周的痰液和骨髓中明显减少。在第9周过敏原激发后7小时，与安慰剂相比，Benralizumab组的痰嗜酸性粒细胞显著减弱（最小二乘均值差异-5.81%，95% CI -10.69--0.94%；p=0.021）；然而，LAR没有明显差异（最小二乘均值差异2.54%，95% CI 3.05-8.12%；p=0.363）。Benralizumab组和安慰剂组分别有 7 人（30.4%）和 14 人（60.9%）出现不良事件。
结论：Benralizumab 给药 8 周后，轻度过敏性哮喘患者血液、骨髓和痰中的嗜酸性粒细胞显著减少；但是，LAR 没有变化，这表明嗜酸性粒细胞本身并不是过敏原诱发支气管收缩的关键因素。
(中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校)
(Eur Respir J. 2024 Sep 12; DOI: 10.1183/13993003.00512-2024)
(Eur Respir J. 2024 Sep 12; DOI: 10.1183/13993003.00512-2024)
Benralizumab for allergic asthma: a randomised, double-blind, placebo-controlled trial
Gauvreau GM, Sehmi R, FitzGerald JM, Leigh R, Cockcroft DW, Davis BE, Mayers I, Boulet LP, Al-Sajee D, Salter BM, Cusack RP, Ho T, Whetstone CE, Alsaji N, Satia I, Killian KJ, Mitchell PD, Magee IP, Bergeron C, Bhutani M, Werkström V, Durżyński T, Shoemaker K, Katial RK, Jison M, Newbold P, McCrae C, O'Byrne PM.
Abstract
Background:Benralizumab induces rapid and near-complete depletion of eosinophils from blood and lung tissue. We investigated whether benralizumab could attenuate the allergen-induced late asthmatic response (LAR) in participants with allergic asthma.
Methods:Participants with allergic asthma who demonstrated increased sputum eosinophils and LAR at screening were randomised to benralizumab 30 mg or matched placebo given every 4 weeks for 8 weeks (3 doses). Allergen challenges were performed at weeks 9 and 12 when blood, sputum, bone marrow and bronchial tissue eosinophils and LAR were assessed.
Results:46 participants (mean age 30.9 years) were randomised to benralizumab (n=23) or placebo (n=23). Eosinophils were significantly reduced in the benralizumab group compared with placebo in blood at 4 weeks and sputum and bone marrow at 9 weeks after treatment initiation. At 7 h after an allergen challenge at week 9, sputum eosinophilia was significantly attenuated in the benralizumab group compared to placebo (least squares mean difference -5.81%, 95% CI -10.69- -0.94%; p=0.021); however, the LAR was not significantly different (least squares mean difference 2.54%, 95% CI 3.05-8.12%; p=0.363). Adverse events were reported for seven (30.4%) and 14 (60.9%) participants in the benralizumab and placebo groups, respectively.
Conclusion:Benralizumab administration over 8 weeks resulted in a significant attenuation of blood, bone marrow and sputum eosinophilia in participants with mild allergic asthma; however, there was no change in the LAR, suggesting that eosinophils alone are not a key component of allergen-induced bronchoconstriction.
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