吸入抗TSLP抗体片段-艾克莱利单抗，来阻断对轻度哮喘过敏原的反应
2023/05/25
摘要
背景：胸腺基质淋巴生成素(TSLP)是驱动过敏性炎症反应的关键上游调节因子。我们使用过敏原吸入激发（AIC）评估了艾克莱利单抗（一种针对人类TSLP的有效吸入中和抗体片段）在轻度特应性哮喘患者中的有效性和安全性。
方法：这是一项为期12周的随机、双盲、安慰剂对照、平行设计、多中心过敏原支气管激发研究，在加拿大和德国的10个中心开展。18-60岁患有稳定轻度特应性哮喘的受试者被随机分配（1：1）接受4mg每日一次吸入性艾克莱利单抗或安慰剂。主要终点是过敏原诱导的晚期哮喘反应（LAR）期间1 s内用力呼气量（FEV）的变化的曲线下面积（AUC），和第84天的最大百分比减少（LAR%）量，以及艾克莱利单抗的安全性。过敏原诱导的早期哮喘反应（EAR）、痰液嗜酸性粒细胞和呼出的一氧化氮分数是次要和探索性的终点。
结果：28名受试者被随机分配到艾克莱利单抗组(n=15)或安慰剂组(n=13)。第84天，艾克莱利单抗组的各项实验指标显著降低：LAR AUC降低 64% (p=0.008)，LAR%降低48% (p=0.029)，致敏原诱生的痰嗜酸粒细胞在致敏后7h降低64% (p=0.011)， 24h降低52% (p=0.047)。艾克莱利单抗也降低了EAR AUC (p=0.097)和EAR% (p=0.105)的指标数值。在整个研究过程中，除过敏原产生后24小时(第43天和第85天)外，各指标水平较基线均显著降低(p<0.05)。总体而言，艾克莱利单抗是安全且可耐受性良好的。
结论：艾克莱利单抗可显著减轻过敏原引起的支气管收缩和呼吸道炎症，且对轻度特应性哮喘患者是安全的。
Inhaled anti-TSLP antibody fragment, ecleralimab, blocks responses to allergen in mild asthma.
Gauvreau GM, Hohlfeld JM, FitzGerald JM,
Abstrast
Background: Thymic stromal lymphopoietin (TSLP) is a key upstream regulator driving allergic inflammatory responses. We evaluated the efficacy and safety of ecleralimab, a potent inhaled neutralising antibody fragment against human TSLP, using allergen inhalation challenge (AIC) in subjects with mild atopic asthma.
Methods: This was a 12-week, randomised, double-blind, placebo-controlled, parallel-design, multicentre allergen bronchoprovocation study conducted at 10 centres across Canada and Germany. Subjects aged 18-60 years with stable mild atopic asthma were randomised (1:1) to receive 4 mg once-daily inhaled ecleralimab or placebo. Primary end-points were the allergen-induced change in forced expiratory volume in 1 s (FEV) during the late asthmatic response (LAR) measured by area under the curve (AUC) and maximum percentage decrease (LAR%) on day 84, and the safety of ecleralimab. Allergen-induced early asthmatic response (EAR), sputum eosinophils and fractional exhaled nitric oxide ( ) were secondary and exploratory end-points.
Results: 28 subjects were randomised to ecleralimab (n=15) or placebo (n=13). On day 84, ecleralimab significantly attenuated LAR AUC by 64% (p=0.008), LAR% by 48% (p=0.029), and allergen-induced sputum eosinophils by 64% at 7 h (p=0.011) and by 52% at 24 h (p=0.047) post-challenge. Ecleralimab also numerically reduced EAR AUC (p=0.097) and EAR% (p=0.105). levels were significantly reduced from baseline throughout the study (p<0.05), except at 24 h post-allergen (day 43 and day 85). Overall, ecleralimab was safe and well tolerated.
Conclusions: Ecleralimab significantly attenuated allergen-induced bronchoconstriction and airway inflammation, and was safe in subjects with mild atopic asthma.
背景：胸腺基质淋巴生成素(TSLP)是驱动过敏性炎症反应的关键上游调节因子。我们使用过敏原吸入激发（AIC）评估了艾克莱利单抗（一种针对人类TSLP的有效吸入中和抗体片段）在轻度特应性哮喘患者中的有效性和安全性。
方法：这是一项为期12周的随机、双盲、安慰剂对照、平行设计、多中心过敏原支气管激发研究，在加拿大和德国的10个中心开展。18-60岁患有稳定轻度特应性哮喘的受试者被随机分配（1：1）接受4mg每日一次吸入性艾克莱利单抗或安慰剂。主要终点是过敏原诱导的晚期哮喘反应（LAR）期间1 s内用力呼气量（FEV）的变化的曲线下面积（AUC），和第84天的最大百分比减少（LAR%）量，以及艾克莱利单抗的安全性。过敏原诱导的早期哮喘反应（EAR）、痰液嗜酸性粒细胞和呼出的一氧化氮分数是次要和探索性的终点。
结果：28名受试者被随机分配到艾克莱利单抗组(n=15)或安慰剂组(n=13)。第84天，艾克莱利单抗组的各项实验指标显著降低：LAR AUC降低 64% (p=0.008)，LAR%降低48% (p=0.029)，致敏原诱生的痰嗜酸粒细胞在致敏后7h降低64% (p=0.011)， 24h降低52% (p=0.047)。艾克莱利单抗也降低了EAR AUC (p=0.097)和EAR% (p=0.105)的指标数值。在整个研究过程中，除过敏原产生后24小时(第43天和第85天)外，各指标水平较基线均显著降低(p<0.05)。总体而言，艾克莱利单抗是安全且可耐受性良好的。
结论：艾克莱利单抗可显著减轻过敏原引起的支气管收缩和呼吸道炎症，且对轻度特应性哮喘患者是安全的。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(Eur Respir J 2023 Mar;61(3) doi: 10.1183/13993003.01193-2022.IF：12.339.)
(Eur Respir J 2023 Mar;61(3) doi: 10.1183/13993003.01193-2022.IF：12.339.)
Inhaled anti-TSLP antibody fragment, ecleralimab, blocks responses to allergen in mild asthma.
Gauvreau GM, Hohlfeld JM, FitzGerald JM,
Abstrast
Background: Thymic stromal lymphopoietin (TSLP) is a key upstream regulator driving allergic inflammatory responses. We evaluated the efficacy and safety of ecleralimab, a potent inhaled neutralising antibody fragment against human TSLP, using allergen inhalation challenge (AIC) in subjects with mild atopic asthma.
Methods: This was a 12-week, randomised, double-blind, placebo-controlled, parallel-design, multicentre allergen bronchoprovocation study conducted at 10 centres across Canada and Germany. Subjects aged 18-60 years with stable mild atopic asthma were randomised (1:1) to receive 4 mg once-daily inhaled ecleralimab or placebo. Primary end-points were the allergen-induced change in forced expiratory volume in 1 s (FEV) during the late asthmatic response (LAR) measured by area under the curve (AUC) and maximum percentage decrease (LAR%) on day 84, and the safety of ecleralimab. Allergen-induced early asthmatic response (EAR), sputum eosinophils and fractional exhaled nitric oxide ( ) were secondary and exploratory end-points.
Results: 28 subjects were randomised to ecleralimab (n=15) or placebo (n=13). On day 84, ecleralimab significantly attenuated LAR AUC by 64% (p=0.008), LAR% by 48% (p=0.029), and allergen-induced sputum eosinophils by 64% at 7 h (p=0.011) and by 52% at 24 h (p=0.047) post-challenge. Ecleralimab also numerically reduced EAR AUC (p=0.097) and EAR% (p=0.105). levels were significantly reduced from baseline throughout the study (p<0.05), except at 24 h post-allergen (day 43 and day 85). Overall, ecleralimab was safe and well tolerated.
Conclusions: Ecleralimab significantly attenuated allergen-induced bronchoconstriction and airway inflammation, and was safe in subjects with mild atopic asthma.
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