严重哮喘的随机对照试验：通过表型或定型进行选择
2020/01/02
摘要
先前文献中经常强调研究试验人群与临床实践人群之间的差异。但目前却没有文章去研究表型靶向生物治疗重症哮喘的随机对照试验(rct)中是否也存在这种差异以及这种差异是如何建立起来的。本实验将威塞克斯严重哮喘队列(WSAC)中342名重症哮喘患者的详细特征数据与2000年以来发表的评估重症哮喘生物治疗的ii期和III期rct的综合试验合格标准进行比较。37个RCT随机对照实验评估了20种生物疗法。只有9.8%的重症哮喘患者(3.5-17.5%)符合三期试验的入组标准。由于对气流阻塞、支气管舒张后气道可逆性和吸烟史的严格规定使得该试验排除了相当多数量的患者。严重嗜酸性粒细胞增多型哮喘患者中有78.9%(范围73.2-86.6%)被排除在白细胞介素(IL)-5/IL- 5r靶向治疗的III期试验之外。在WSAC的研究中，除了纳入的特征明显且在专家诊疗下得到最佳治疗的重症哮喘患者，绝大多数患者因为“其纳入标准是确认诊断而不是预测治疗所涉及的生物标志物”而被排除在试验参与之外。
Randomised controlled trials in severe asthma: selection by phenotype or stereotype
Thomas Brown et al. Eur Respir J. 2018 Dec 13
Abstract
Previous publications have highlighted the disparity between research trial populations and those in clinical practice, but it has not been established how this relates to randomised controlled trials (RCTs) of phenotype-targeted biological therapies in severe asthma.
Detailed characterisation data for 342 severe asthma patients within the Wessex Severe Asthma Cohort (WSAC) was compared against comprehensive trial eligibility criteria for published phase IIB and phase III RCTs evaluating biological therapies in severe asthma since 2000.
37 RCTs evaluating 20 biological therapies were identified. Only a median of 9.8% (range 3.5–17.5%) of severe asthma patients were found to be eligible for enrolment in the phase III trials. Stipulations for airflow obstruction, bronchodilator reversibility and smoking history excluded significant numbers of patients. A median of 78.9% (range 73.2–86.6%) of patients with severe eosinophilic asthma would have been excluded from participation in the phase III licensing trials of interleukin (IL)-5/IL-5R targeted therapies.
Despite including only well characterised and optimally treated severe asthmatics under specialist care within the WSAC study, the vast majority were excluded from trial participation by criteria designed to re-confirm diagnostic labels rather than by biomarker criteria that predict the characteristic addressed by the treatment.
先前文献中经常强调研究试验人群与临床实践人群之间的差异。但目前却没有文章去研究表型靶向生物治疗重症哮喘的随机对照试验(rct)中是否也存在这种差异以及这种差异是如何建立起来的。本实验将威塞克斯严重哮喘队列(WSAC)中342名重症哮喘患者的详细特征数据与2000年以来发表的评估重症哮喘生物治疗的ii期和III期rct的综合试验合格标准进行比较。37个RCT随机对照实验评估了20种生物疗法。只有9.8%的重症哮喘患者(3.5-17.5%)符合三期试验的入组标准。由于对气流阻塞、支气管舒张后气道可逆性和吸烟史的严格规定使得该试验排除了相当多数量的患者。严重嗜酸性粒细胞增多型哮喘患者中有78.9%(范围73.2-86.6%)被排除在白细胞介素(IL)-5/IL- 5r靶向治疗的III期试验之外。在WSAC的研究中，除了纳入的特征明显且在专家诊疗下得到最佳治疗的重症哮喘患者，绝大多数患者因为“其纳入标准是确认诊断而不是预测治疗所涉及的生物标志物”而被排除在试验参与之外。
(中国医科大学附属一院呼吸与危重症学科 李文扬 摘译 杨冬 审校)
(Thomas Brown et al. Eur Respir J. 2018 Dec 13)
(Thomas Brown et al. Eur Respir J. 2018 Dec 13)
Randomised controlled trials in severe asthma: selection by phenotype or stereotype
Thomas Brown et al. Eur Respir J. 2018 Dec 13
Abstract
Previous publications have highlighted the disparity between research trial populations and those in clinical practice, but it has not been established how this relates to randomised controlled trials (RCTs) of phenotype-targeted biological therapies in severe asthma.
Detailed characterisation data for 342 severe asthma patients within the Wessex Severe Asthma Cohort (WSAC) was compared against comprehensive trial eligibility criteria for published phase IIB and phase III RCTs evaluating biological therapies in severe asthma since 2000.
37 RCTs evaluating 20 biological therapies were identified. Only a median of 9.8% (range 3.5–17.5%) of severe asthma patients were found to be eligible for enrolment in the phase III trials. Stipulations for airflow obstruction, bronchodilator reversibility and smoking history excluded significant numbers of patients. A median of 78.9% (range 73.2–86.6%) of patients with severe eosinophilic asthma would have been excluded from participation in the phase III licensing trials of interleukin (IL)-5/IL-5R targeted therapies.
Despite including only well characterised and optimally treated severe asthmatics under specialist care within the WSAC study, the vast majority were excluded from trial participation by criteria designed to re-confirm diagnostic labels rather than by biomarker criteria that predict the characteristic addressed by the treatment.
上一篇：
哮喘儿童上呼吸道微生物群和哮喘控制丧失的关系
下一篇：
使用植物花粉片剂进行免疫治疗可减少过敏性鼻炎和哮喘的药物使用：一项来自法国的回顾性数据库研究
