重症哮喘的随机对照试验：表型或定型选择
2018/11/14
摘要
背景：之前研究强调了研究试验人群与临床实践之间的差异，但尚未确定这与重症哮喘中表型靶向生物疗法的随机对照试验（RCT）有何关联。
方法：Wessex重症哮喘队列（WSAC）中342名重症哮喘患者的详细特征数据与自2000年以来评估重症哮喘生物治疗的已发表IIB期和III期RCT的综合试验资格标准进行了比较。
结果：确定了37项评估20种生物疗法的RCT。只有9.8％（中位数;范围3.5％-17.5％）的重症哮喘患者有资格参加III期临床试验。气流阻塞，支气管扩张剂可逆性和吸烟史的规定排除了大量患者。重症嗜酸性粒细胞哮喘患者的78.9％（中位数;范围73.2％-86.6％）将被排除在参与IL-5/5R靶向治疗的III期许可试验之外。
结论：尽管在Wessex重症哮喘队列研究中仅包括经过专门护理的良好特征和最佳治疗的重症哮喘患者，但绝大多数被排除在试验参与之外，其标准旨在重新确认诊断标签，而不是通过预测治疗所解决的特征的生物标志物标准。
Randomised Controlled Trials in Severe Asthma: Selection by Phenotype or Stereotype.
Brown T, Jones T, Gove K, Barber C, Elliott S, Chauhan A, Howarth P; Wessex Severe Asthma Cohort team: L Aitkin, S Babu, P Dennison, R Djukanovic, C Grainge, L Hewitt, N Jayasekera, R Kurukulaaratchy, S Kerley, L Lau, D Laws, J Owen, E Ray, D Reynish, H Rupani and O Scullion-Win.
Abstract
BACKGROUND:Previous publications have highlighted the disparity between research trial populations and clinical practise but it is not established how this relates to randomised controlled trials (RCTs) of phenotype targeted biological therapies in severe asthma.
METHODS: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 III RCTs evaluating biological therapies in severe asthma since 2000.
RESULTS:37 RCTs evaluating 20 biological therapies were identified. Only 9.8% (median; range 3.5%-17.5%) of severe asthma patients would have been eligible for enrolment in the phase III trials. Stipulations for airflow obstruction, bronchodilator reversibility and smoking history exclude significant numbers of patients. 78.9% (median; range 73.2%-86.6%) of patients with severe eosinophilic asthma would have been excluded from participation in the phase III licensing trials of IL-5/5R targeted therapies.
CONCLUSIONS:Despite including only well characterised and optimally treated severe asthmatics under specialist care within the Wessex Severe Asthma Cohort 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.
背景：之前研究强调了研究试验人群与临床实践之间的差异，但尚未确定这与重症哮喘中表型靶向生物疗法的随机对照试验（RCT）有何关联。
方法：Wessex重症哮喘队列（WSAC）中342名重症哮喘患者的详细特征数据与自2000年以来评估重症哮喘生物治疗的已发表IIB期和III期RCT的综合试验资格标准进行了比较。
结果：确定了37项评估20种生物疗法的RCT。只有9.8％（中位数;范围3.5％-17.5％）的重症哮喘患者有资格参加III期临床试验。气流阻塞，支气管扩张剂可逆性和吸烟史的规定排除了大量患者。重症嗜酸性粒细胞哮喘患者的78.9％（中位数;范围73.2％-86.6％）将被排除在参与IL-5/5R靶向治疗的III期许可试验之外。
结论：尽管在Wessex重症哮喘队列研究中仅包括经过专门护理的良好特征和最佳治疗的重症哮喘患者，但绝大多数被排除在试验参与之外，其标准旨在重新确认诊断标签，而不是通过预测治疗所解决的特征的生物标志物标准。
(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)
(Eur Respir J. 2018 Oct 25. pii: 1801444. doi: 10.1183/13993003.01444-2018. [Epub ahead of print])
(Eur Respir J. 2018 Oct 25. pii: 1801444. doi: 10.1183/13993003.01444-2018. [Epub ahead of print])
Randomised Controlled Trials in Severe Asthma: Selection by Phenotype or Stereotype.
Brown T, Jones T, Gove K, Barber C, Elliott S, Chauhan A, Howarth P; Wessex Severe Asthma Cohort team: L Aitkin, S Babu, P Dennison, R Djukanovic, C Grainge, L Hewitt, N Jayasekera, R Kurukulaaratchy, S Kerley, L Lau, D Laws, J Owen, E Ray, D Reynish, H Rupani and O Scullion-Win.
Abstract
BACKGROUND:Previous publications have highlighted the disparity between research trial populations and clinical practise but it is not established how this relates to randomised controlled trials (RCTs) of phenotype targeted biological therapies in severe asthma.
METHODS: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 III RCTs evaluating biological therapies in severe asthma since 2000.
RESULTS:37 RCTs evaluating 20 biological therapies were identified. Only 9.8% (median; range 3.5%-17.5%) of severe asthma patients would have been eligible for enrolment in the phase III trials. Stipulations for airflow obstruction, bronchodilator reversibility and smoking history exclude significant numbers of patients. 78.9% (median; range 73.2%-86.6%) of patients with severe eosinophilic asthma would have been excluded from participation in the phase III licensing trials of IL-5/5R targeted therapies.
CONCLUSIONS:Despite including only well characterised and optimally treated severe asthmatics under specialist care within the Wessex Severe Asthma Cohort 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：
Dupilumab在糖皮质激素依赖性重症哮喘中的疗效和安全性
下一篇：
综合方法确定不同哮喘患者的皮质类固醇反应变异
