2型哮喘单克隆抗体的系统评价及网络meta分析
2020/02/11
摘要
在针对2型哮喘中嗜酸性粒细胞炎症的新治疗方法逐渐兴起的背景下，我们旨在使用荟萃分析评估单克隆抗体降低恶化率的疗效。我们在PubMed和Web of Science上搜索针对2型相关哮喘关键介质的单克隆抗体的II期和III期随机临床试验。选择涉及IL-5途径、IL-13、IL-4和IL-13共同受体、IL-9、IL-2和TSLP的生物制剂的30个试验。因为在文献中未检索到严格对照试验，我们用网络荟萃分析比较不同的治疗方法对恶化率的影响。
与安慰剂相比，美波利珠单抗、瑞利珠单抗和贝那利珠单抗显著降低了急性加重的风险（分别降低47-52%、50-60%和28-51%）。瑞利珠单抗和贝那利珠单抗也能改善肺功能。杜皮鲁单抗和替泽普卢单抗可改善频繁出现急性加重患者的肺功能。Lebrikizumab对病情急性加重次数、症状控制及与健康相关的生活质量无显著影响。与安慰剂相比，Tralokinumab可以改善肺功能。所有治疗组和安慰剂组的网络荟萃分析显示，没有一种生物制剂优于其他生物制剂。与安慰剂相比，单克隆抗体大大降低了病情恶化率，尽管在IL-5作用药物的亚组分析中，与安慰剂相比，只有贝那利单抗（n= 2051）被证实可以显著降低急性发作频率。
在已发表的试验中，研究者已证明诸如美泊利珠单抗，瑞利珠单抗和贝那利珠单抗的单克隆抗体可降低严重持续性嗜酸性粒细胞性哮喘的恶化率。然而，在网络荟萃分析中，我们没有观察到任何一种生物制剂在统计学上有显著优势。因此还需要进行更多直接的严格对照研究和更明确的内型研究。
Monoclonal antibodies in type 2 asthma: a systematic review and network meta-analysis
Respir Res. 2019 Aug 8;20(1):179
Abstract
Since novel treatments to target eosinophilic inflammation in Type 2 asthma are emerging, we aimed to evaluate and meta-analyze the efficacy of monoclonal antibodies to reduce exacerbation rate. PubMed and Web of Science were searched for phase II and phase III randomized clinical trials with monoclonal antibodies targeting key mediators of type 2-associated asthma. Thirty trials were selected involving biologics that target the IL-5 pathway, IL-13, the common IL-4 and IL-13 receptor, IL-9, IL-2 and TSLP. As no head-to-head trials were retrieved from literature, we performed an arm-based network meta-analysis to compare effects on exacerbation rate between the different treatments.
Mepolizumab, reslizumab and benralizumab significantly reduced the risk of exacerbations compared to placebo (by 47–52%, 50–60%, and 28–51% respectively). Reslizumab and benralizumab also improved lung function. Dupilumab and tezepelumab improved lung function in frequent exacerbators. Lebrikizumab had no significant effect on the number of exacerbations, symptom control or health-related quality of life. Tralokinumab improved lung function compared to placebo. Network meta-analysis of all treatment and placebo arms, showed no superiority of one biologic over the others. Large reductions in exacerbation rates were observed compared to placebo, though only benralizumab was sufficiently powered (n = 2051) to demonstrate significantly decreased exacerbation rates in the subgroup analysis of IL-5 acting agents compared to placebo.
Monoclonal antibodies such as mepolizumab, reslizumab and benralizumab have proven their benefit to reduce exacerbation rates in severe persistent eosinophilic asthma in the published trials. However, no statistically significant superiority was observed of one biologic over the other in the network meta-analysis. More studies with direct head to head comparisons and better defined endotypes are required.
在针对2型哮喘中嗜酸性粒细胞炎症的新治疗方法逐渐兴起的背景下，我们旨在使用荟萃分析评估单克隆抗体降低恶化率的疗效。我们在PubMed和Web of Science上搜索针对2型相关哮喘关键介质的单克隆抗体的II期和III期随机临床试验。选择涉及IL-5途径、IL-13、IL-4和IL-13共同受体、IL-9、IL-2和TSLP的生物制剂的30个试验。因为在文献中未检索到严格对照试验，我们用网络荟萃分析比较不同的治疗方法对恶化率的影响。
与安慰剂相比，美波利珠单抗、瑞利珠单抗和贝那利珠单抗显著降低了急性加重的风险（分别降低47-52%、50-60%和28-51%）。瑞利珠单抗和贝那利珠单抗也能改善肺功能。杜皮鲁单抗和替泽普卢单抗可改善频繁出现急性加重患者的肺功能。Lebrikizumab对病情急性加重次数、症状控制及与健康相关的生活质量无显著影响。与安慰剂相比，Tralokinumab可以改善肺功能。所有治疗组和安慰剂组的网络荟萃分析显示，没有一种生物制剂优于其他生物制剂。与安慰剂相比，单克隆抗体大大降低了病情恶化率，尽管在IL-5作用药物的亚组分析中，与安慰剂相比，只有贝那利单抗（n= 2051）被证实可以显著降低急性发作频率。
在已发表的试验中，研究者已证明诸如美泊利珠单抗，瑞利珠单抗和贝那利珠单抗的单克隆抗体可降低严重持续性嗜酸性粒细胞性哮喘的恶化率。然而，在网络荟萃分析中，我们没有观察到任何一种生物制剂在统计学上有显著优势。因此还需要进行更多直接的严格对照研究和更明确的内型研究。
（中国医科大学附属第一医院 李文扬 摘译 杨冬 审校）
（Respir Res. 2019 Aug 8;20(1):179）
（Respir Res. 2019 Aug 8;20(1):179）
Monoclonal antibodies in type 2 asthma: a systematic review and network meta-analysis
Respir Res. 2019 Aug 8;20(1):179
Abstract
Since novel treatments to target eosinophilic inflammation in Type 2 asthma are emerging, we aimed to evaluate and meta-analyze the efficacy of monoclonal antibodies to reduce exacerbation rate. PubMed and Web of Science were searched for phase II and phase III randomized clinical trials with monoclonal antibodies targeting key mediators of type 2-associated asthma. Thirty trials were selected involving biologics that target the IL-5 pathway, IL-13, the common IL-4 and IL-13 receptor, IL-9, IL-2 and TSLP. As no head-to-head trials were retrieved from literature, we performed an arm-based network meta-analysis to compare effects on exacerbation rate between the different treatments.
Mepolizumab, reslizumab and benralizumab significantly reduced the risk of exacerbations compared to placebo (by 47–52%, 50–60%, and 28–51% respectively). Reslizumab and benralizumab also improved lung function. Dupilumab and tezepelumab improved lung function in frequent exacerbators. Lebrikizumab had no significant effect on the number of exacerbations, symptom control or health-related quality of life. Tralokinumab improved lung function compared to placebo. Network meta-analysis of all treatment and placebo arms, showed no superiority of one biologic over the others. Large reductions in exacerbation rates were observed compared to placebo, though only benralizumab was sufficiently powered (n = 2051) to demonstrate significantly decreased exacerbation rates in the subgroup analysis of IL-5 acting agents compared to placebo.
Monoclonal antibodies such as mepolizumab, reslizumab and benralizumab have proven their benefit to reduce exacerbation rates in severe persistent eosinophilic asthma in the published trials. However, no statistically significant superiority was observed of one biologic over the other in the network meta-analysis. More studies with direct head to head comparisons and better defined endotypes are required.
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重症哮喘患者长期阿奇霉素治疗可减少流感嗜血杆菌感染，增加了抗生素耐药性
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转换为等效吸入装置的成本节约及其对健康结果的影响
