噻托溴铵呼吸道附加物在症状性哮喘中有效，不依赖于T2表型
2017/12/20
摘要
背景：在有或没有长效β2受体激动剂（LABA）的情况下，将噻托溴铵添加到现有的吸入性皮质类固醇（ICS）维持治疗中已显示对症状性哮喘患者有益。评估对噻托溴铵呼吸道附加治疗的反应是否受到患者T2状态的影响。
方法：在此探索性研究中，分析来自4个III期试验的数据：每日一次噻托溴铵5μg或安慰剂，作为ICS + LABA的附加物（PrimoTinA-哮喘；2次重复试验；NCT00772538 / NCT00776984；n = 912）；每日一次噻托溴铵5μg或2.5μg，每日两次沙美特罗50μg或安慰剂作为ICS的附加物（MezzoTinA-哮喘；2次重复试验；NCT01172808 / NCT01172821； n = 2100）。先前已经报道了这些研究预先设定的有效性结果。在这里，进行进一步的探索性亚组分析以研究这些共同终点是否受血清IgE水平，血液嗜酸性粒细胞计数和临床医师对过敏性哮喘的判断的影响。此外，对于连续参数，即IgE和血液嗜酸性粒细胞，它们对治疗效果的影响是在整个范围内建模的。
结果:噻托溴铵在改善FEV1峰值后3小时内有效，并且不受T2状态的影响。噻托溴铵显着降低重症哮喘发作和哮喘加重的风险，独立于T2表型；Cox回归建模支持噻托溴铵对哮喘发作的有益作用，独立于IgE水平或嗜酸性粒细胞计数。在高T2和低T2患者中观察到噻托溴铵比安慰剂7个问题的哮喘控制问卷（ACQ-7）响应率的数值有改善；逻辑回归建模为噻托溴铵治疗提供了进一步的证据，可以改善ACQ-7应答率，而不依赖于IgE水平或嗜酸性粒细胞计数。
结论：我们探索性分析的结果表明，噻托溴铵作为ICS±LABA呼吸道附加物对症状性哮喘患者的肺功能，发作风险和症状控制的改善不依赖于T2表型。
Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype.
Casale TB1, Bateman ED2, Vandewalker M3, Virchow JC4, Schmidt H5, Engel M6, Moroni-Zentgraf P7, Kerstjens HAM8.
Abstract
BACKGROUND:Adding tiotropium to existing inhaled corticosteroid (ICS) maintenance therapy with or without a long-acting β2-agonist (LABA) has been shown to be beneficial in patients with symptomatic asthma. To assess whether responses to tiotropium Respimat add-on therapy were influenced by patients' T2 status.
METHODS:In this exploratory study, data from 4 phase III trials were analyzed: once-daily tiotropium 5 μg or placebo as add-on to ICS + LABA (PrimoTinA-asthma; 2 replicate trials; NCT00772538/NCT00776984; n = 912); once-daily tiotropium 5 μg or 2.5 μg, twice-daily salmeterol 50 μg, or placebo as add-on to ICS (MezzoTinA-asthma; 2 replicate trials; NCT01172808/NCT01172821; n = 2100). The prespecified efficacy outcomes of these studies have been reported previously. Here, further exploratory subgroup analyses were performed to study whether these coprimary end points were influenced by serum IgE levels, blood eosinophil counts, and clinician judgment of allergic asthma. In addition, for the continuous parameters, namely, IgE and blood eosinophils, their influence on the treatment effect was modeled over the whole range of values.
RESULTS:Tiotropium was efficacious in improving peak FEV1 within 3 hours postdose and trough FEV1, independent of T2 status. Tiotropium significantly reduced the risk of severe asthma exacerbations and asthma worsening, independent of T2 phenotype; Cox regression modeling supported a beneficial effect of tiotropium on exacerbations, independent of IgE levels or eosinophil counts. Numerical improvements in the 7-question Asthma Control Questionnaire (ACQ-7) responder rate with tiotropium versus placebo were observed in T2high and T2low patients; logistic regression modeling provided further evidence for improvement in ACQ-7 responder rates with tiotropium, independent of IgE levels or eosinophil counts.
CONCLUSIONS:The results of our exploratory analyses suggest that the improvements seen with tiotropium Respimat as add-on to ICS ± LABA in patients with symptomatic asthma on lung function, exacerbation risk, and symptom control are independent of T2 phenotype.
背景：在有或没有长效β2受体激动剂（LABA）的情况下，将噻托溴铵添加到现有的吸入性皮质类固醇（ICS）维持治疗中已显示对症状性哮喘患者有益。评估对噻托溴铵呼吸道附加治疗的反应是否受到患者T2状态的影响。
方法：在此探索性研究中，分析来自4个III期试验的数据：每日一次噻托溴铵5μg或安慰剂，作为ICS + LABA的附加物（PrimoTinA-哮喘；2次重复试验；NCT00772538 / NCT00776984；n = 912）；每日一次噻托溴铵5μg或2.5μg，每日两次沙美特罗50μg或安慰剂作为ICS的附加物（MezzoTinA-哮喘；2次重复试验；NCT01172808 / NCT01172821； n = 2100）。先前已经报道了这些研究预先设定的有效性结果。在这里，进行进一步的探索性亚组分析以研究这些共同终点是否受血清IgE水平，血液嗜酸性粒细胞计数和临床医师对过敏性哮喘的判断的影响。此外，对于连续参数，即IgE和血液嗜酸性粒细胞，它们对治疗效果的影响是在整个范围内建模的。
结果:噻托溴铵在改善FEV1峰值后3小时内有效，并且不受T2状态的影响。噻托溴铵显着降低重症哮喘发作和哮喘加重的风险，独立于T2表型；Cox回归建模支持噻托溴铵对哮喘发作的有益作用，独立于IgE水平或嗜酸性粒细胞计数。在高T2和低T2患者中观察到噻托溴铵比安慰剂7个问题的哮喘控制问卷（ACQ-7）响应率的数值有改善；逻辑回归建模为噻托溴铵治疗提供了进一步的证据，可以改善ACQ-7应答率，而不依赖于IgE水平或嗜酸性粒细胞计数。
结论：我们探索性分析的结果表明，噻托溴铵作为ICS±LABA呼吸道附加物对症状性哮喘患者的肺功能，发作风险和症状控制的改善不依赖于T2表型。
(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 Pract. 2017 Nov 22. pii: S2213-2198(17)30721-3. doi: 10.1016/j.jaip.2017.08.037. [Epub ahead of print])
(J Allergy Clin Immunol Pract. 2017 Nov 22. pii: S2213-2198(17)30721-3. doi: 10.1016/j.jaip.2017.08.037. [Epub ahead of print])
Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype.
Casale TB1, Bateman ED2, Vandewalker M3, Virchow JC4, Schmidt H5, Engel M6, Moroni-Zentgraf P7, Kerstjens HAM8.
Abstract
BACKGROUND:Adding tiotropium to existing inhaled corticosteroid (ICS) maintenance therapy with or without a long-acting β2-agonist (LABA) has been shown to be beneficial in patients with symptomatic asthma. To assess whether responses to tiotropium Respimat add-on therapy were influenced by patients' T2 status.
METHODS:In this exploratory study, data from 4 phase III trials were analyzed: once-daily tiotropium 5 μg or placebo as add-on to ICS + LABA (PrimoTinA-asthma; 2 replicate trials; NCT00772538/NCT00776984; n = 912); once-daily tiotropium 5 μg or 2.5 μg, twice-daily salmeterol 50 μg, or placebo as add-on to ICS (MezzoTinA-asthma; 2 replicate trials; NCT01172808/NCT01172821; n = 2100). The prespecified efficacy outcomes of these studies have been reported previously. Here, further exploratory subgroup analyses were performed to study whether these coprimary end points were influenced by serum IgE levels, blood eosinophil counts, and clinician judgment of allergic asthma. In addition, for the continuous parameters, namely, IgE and blood eosinophils, their influence on the treatment effect was modeled over the whole range of values.
RESULTS:Tiotropium was efficacious in improving peak FEV1 within 3 hours postdose and trough FEV1, independent of T2 status. Tiotropium significantly reduced the risk of severe asthma exacerbations and asthma worsening, independent of T2 phenotype; Cox regression modeling supported a beneficial effect of tiotropium on exacerbations, independent of IgE levels or eosinophil counts. Numerical improvements in the 7-question Asthma Control Questionnaire (ACQ-7) responder rate with tiotropium versus placebo were observed in T2high and T2low patients; logistic regression modeling provided further evidence for improvement in ACQ-7 responder rates with tiotropium, independent of IgE levels or eosinophil counts.
CONCLUSIONS:The results of our exploratory analyses suggest that the improvements seen with tiotropium Respimat as add-on to ICS ± LABA in patients with symptomatic asthma on lung function, exacerbation risk, and symptom control are independent of T2 phenotype.
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