mepolizumab在嗜酸性粒细胞表型的重症哮喘患儿中的长期安全性和药效学
2019/09/09
摘要
背景：Mepolizumab被批准用于年龄≥12（美国）或≥6（欧盟）岁的嗜酸性粒细胞表型的重症哮喘患者，但尚未评估其在6-11岁儿童中的长期使用。本文旨在评估mepolizumab对6-11岁嗜酸性粒细胞表型的重症哮喘患儿的长期安全性，有效性和药效学。
方法：在这项开放标签、非对照及重复剂量延伸研究（NCT02377427）中，6-11岁嗜酸性粒细胞表型重症哮喘患儿（筛查时血液嗜酸性粒细胞计数≥150细胞/μL或前一年≥300细胞/μL） 在52周内接受体重依赖剂量的皮下注射mepolizumab 40 mg（<40 kg）或100 mg（≥40kg）。 终点包括不良事件（AEs）和免疫原性（主要结局），绝对血液嗜酸性粒细胞计数（细胞/μL）（次要结局）和年化恶化率和哮喘控制问卷/儿童哮喘控制测试分数（探索性结局）的发生率。
结果：52周内，30名儿童接受了mepolizumab，27名（90％）和7名（23％）分别出现治疗中的AEs和严重的AEs。 没有与治疗有关的SAEs，没有致命的AEs，没有明显的特定AEs模式，也没有报道抗药物抗体或中和抗体反应。 与基线值相比，mepolizumab治疗减少了血液嗜酸性粒细胞计数和哮喘急性发作，并改善了所有治疗组的哮喘控制。
结论：该研究的长期安全性、药效学和有效性数据支持mepolizumab在嗜酸性粒细胞表型重症哮喘患儿中的正效益风险特征，并且与成人和青少年研究中的数据相似。
Long-term safety and pharmacodynamics of mepolizumab in children with severe asthma with an eosinophilic phenotype.
Gupta A, Ikeda M, Geng B, Azmi J, Price RG, Bradford ES, Yancey SW, Steinfeld J.
Abstract
BACKGROUND:Mepolizumab is approved for patients with severe asthma with an eosinophilic phenotype aged ≥12 (US) or ≥6 (EU) years, but its long-term use in children aged 6-11 years has not yet been assessed. To assess the long-term safety, efficacy, and pharmacodynamics of mepolizumab in children aged 6-11 years with severe asthma with an eosinophilic phenotype.
METHODS:In this open-label, uncontrolled, repeat-dose extension study (NCT02377427), children aged 6-11 years with severe asthma with an eosinophilic phenotype (blood eosinophil counts ≥150 cells/μL at screening or ≥300 cells/μL in the previous year) received a body weight-dependent dose of subcutaneous mepolizumab 40 mg (<40 kg) or 100 mg (≥40 kg) over 52 weeks. Endpoints included the incidence of adverse events (AEs) and immunogenicity (primary), absolute blood eosinophil count (cells/μL) (secondary) and annualized exacerbation rates and asthma control questionnaire/childhood asthma control test scores (exploratory).
RESULTS:Over 52 weeks, thirty children received mepolizumab; 27 (90%) and 7 (23%) experienced on-treatment AEs and serious AEs, respectively. No SAEs were treatment-related. There were no fatal AEs. No specific patterns of AEs were evident, and no anti-drug antibody or neutralizing antibody responses were reported. Compared with baseline values, mepolizumab treatment reduced blood eosinophil counts and asthma exacerbations, and improved asthma control across all treatment groups.
CONCLUSIONS:The long-term safety, pharmacodynamic and efficacy data from this study support a positive benefit-risk profile for mepolizumab in children with severe asthma with an eosinophilic phenotype and were similar to data in studies in adults and adolescents.
背景：Mepolizumab被批准用于年龄≥12（美国）或≥6（欧盟）岁的嗜酸性粒细胞表型的重症哮喘患者，但尚未评估其在6-11岁儿童中的长期使用。本文旨在评估mepolizumab对6-11岁嗜酸性粒细胞表型的重症哮喘患儿的长期安全性，有效性和药效学。
方法：在这项开放标签、非对照及重复剂量延伸研究（NCT02377427）中，6-11岁嗜酸性粒细胞表型重症哮喘患儿（筛查时血液嗜酸性粒细胞计数≥150细胞/μL或前一年≥300细胞/μL） 在52周内接受体重依赖剂量的皮下注射mepolizumab 40 mg（<40 kg）或100 mg（≥40kg）。 终点包括不良事件（AEs）和免疫原性（主要结局），绝对血液嗜酸性粒细胞计数（细胞/μL）（次要结局）和年化恶化率和哮喘控制问卷/儿童哮喘控制测试分数（探索性结局）的发生率。
结果：52周内，30名儿童接受了mepolizumab，27名（90％）和7名（23％）分别出现治疗中的AEs和严重的AEs。 没有与治疗有关的SAEs，没有致命的AEs，没有明显的特定AEs模式，也没有报道抗药物抗体或中和抗体反应。 与基线值相比，mepolizumab治疗减少了血液嗜酸性粒细胞计数和哮喘急性发作，并改善了所有治疗组的哮喘控制。
结论：该研究的长期安全性、药效学和有效性数据支持mepolizumab在嗜酸性粒细胞表型重症哮喘患儿中的正效益风险特征，并且与成人和青少年研究中的数据相似。
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2019 Aug 16. pii: S0091-6749(19)31046-2. doi: 10.1016/j.jaci.2019.08.005. [Epub ahead of print])
(J Allergy Clin Immunol. 2019 Aug 16. pii: S0091-6749(19)31046-2. doi: 10.1016/j.jaci.2019.08.005. [Epub ahead of print])
Long-term safety and pharmacodynamics of mepolizumab in children with severe asthma with an eosinophilic phenotype.
Gupta A, Ikeda M, Geng B, Azmi J, Price RG, Bradford ES, Yancey SW, Steinfeld J.
Abstract
BACKGROUND:Mepolizumab is approved for patients with severe asthma with an eosinophilic phenotype aged ≥12 (US) or ≥6 (EU) years, but its long-term use in children aged 6-11 years has not yet been assessed. To assess the long-term safety, efficacy, and pharmacodynamics of mepolizumab in children aged 6-11 years with severe asthma with an eosinophilic phenotype.
METHODS:In this open-label, uncontrolled, repeat-dose extension study (NCT02377427), children aged 6-11 years with severe asthma with an eosinophilic phenotype (blood eosinophil counts ≥150 cells/μL at screening or ≥300 cells/μL in the previous year) received a body weight-dependent dose of subcutaneous mepolizumab 40 mg (<40 kg) or 100 mg (≥40 kg) over 52 weeks. Endpoints included the incidence of adverse events (AEs) and immunogenicity (primary), absolute blood eosinophil count (cells/μL) (secondary) and annualized exacerbation rates and asthma control questionnaire/childhood asthma control test scores (exploratory).
RESULTS:Over 52 weeks, thirty children received mepolizumab; 27 (90%) and 7 (23%) experienced on-treatment AEs and serious AEs, respectively. No SAEs were treatment-related. There were no fatal AEs. No specific patterns of AEs were evident, and no anti-drug antibody or neutralizing antibody responses were reported. Compared with baseline values, mepolizumab treatment reduced blood eosinophil counts and asthma exacerbations, and improved asthma control across all treatment groups.
CONCLUSIONS:The long-term safety, pharmacodynamic and efficacy data from this study support a positive benefit-risk profile for mepolizumab in children with severe asthma with an eosinophilic phenotype and were similar to data in studies in adults and adolescents.
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