中重度哮喘患者发作病史对dupilumab临床疗效的影响
2021/07/28
摘要
背景：在未控制的中重度哮喘患者进行的3期QUEST研究（NCT02414854）证明了每2周服用200和300毫克dupilumab与安慰剂相比具有有效性和安全性。这项事后分析评估了dupilumab在2型哮喘患者的发作病史中对有效性终点和哮喘控制的影响。
方法：本研究在过去1年急性发作次数≥1、≥2或≥3次的患者中，对52周治疗期间的年化重度发作频率、12/52周的支气管扩张剂前1秒用力呼气量（FEV1）和24/52周的5项哮喘控制问卷（ACQ-5）评分进行了评估。亚组分层基于基线血嗜酸性粒细胞≥150或≥300个细胞·μL-1或基线分数呼出的一氧化氮≥25 ppb和基线吸入皮质类固醇剂量。
结果：在所有2型哮喘亚组中，dupilumab与安慰剂相比，重度急性发作显著降低了54%至90%，在进入研究前急性发作次数更多的患者改善更大。同样，与安慰剂相比，所有亚组中都观察到FEV1（与安慰剂组比较的最小二乘法[LS]差异：≥1次急性发作组，0.15比0.25；≥2次急性发作组，0.12比0.32；≥3次急性发作组，0.09比0.38；多数p<0.05）和ACQ-5评分（LS平均差异范围：≥1次急性发作组，-0.30至-0.57；≥2次急性发作组，-0.29至-0.56；≥3次急性发作组，-0.43至-0.61；均p<0.05）的改善，与既往急性发作病史无关。
结论：在2型生物标志物升高的哮喘患者中，无论急性发作病史和基线ICS吸入剂量如何，dupilumab均能显著降低重度急性发作，改善FEV1和哮喘控制。
Effect of exacerbation history on clinical response to dupilumab in moderate-severe uncontrolled asthma
Jonathan Corren, Constance H Katelaris, Mario Castro, Jorge F Maspero, Linda B Ford, David M G Halpin, Megan S Rice, Amr Radwan, Yamo Deniz, Paul Rowe, Ariel Teper, Michel Djandji
Abstract
BACKGROUND:The phase 3 QUEST study (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma has demonstrated the efficacy and safety of dupilumab 200 and 300 mg every 2 weeks versus placebo. This post hoc analysis assessed the effect of dupilumab on efficacy outcomes and asthma control across a range of historical exacerbation rates in patients with type 2-high asthma.
METHODS:Annualised severe exacerbation rates over the 52-week treatment period, pre-bronchodilator forced expiratory volume in 1 s (FEV1) at weeks 12/52, and the 5-item Asthma Control Questionnaire (ACQ-5) score at 24/52 were assessed in patients with ≥1, ≥2, or ≥3 exacerbations in the previous year. Subgroups were stratified by baseline blood eosinophils ≥150 or ≥300 cells·μL-1 or baseline fractional exhaled nitric oxide ≥25 ppb and baseline inhaled corticosteroid dose.
RESULTS:Across all type 2-high subgroups, dupilumab versus placebo significantly reduced severe exacerbations by 54 to 90%, with greater improvements in patients with more exacerbations prior to study initiation. Similarly, improvements in FEV1 (least squares [LS] difference versus placebo: ≥1 exacerbation, 0.15 to 0.25 L; ≥2 exacerbations, 0.12 to 0.32 L; ≥3 exacerbations, 0.09 to 0.38 L; majority p<0.05) and ACQ-5 score (LS mean difference range: ≥1 exacerbation, -0.30 to -0.57; ≥2 exacerbations, -0.29 to -0.56; ≥3 exacerbations, -0.43 to -0.61; all p<0.05) were observed, irrespective of prior exacerbation history, across all subgroups.
CONCLUSIONS:Dupilumab significantly reduced severe exacerbations and improved FEV1 and asthma control in patients with elevated type 2 biomarkers irrespective of exacerbation history and baseline ICS dose.
背景：在未控制的中重度哮喘患者进行的3期QUEST研究（NCT02414854）证明了每2周服用200和300毫克dupilumab与安慰剂相比具有有效性和安全性。这项事后分析评估了dupilumab在2型哮喘患者的发作病史中对有效性终点和哮喘控制的影响。
方法：本研究在过去1年急性发作次数≥1、≥2或≥3次的患者中，对52周治疗期间的年化重度发作频率、12/52周的支气管扩张剂前1秒用力呼气量（FEV1）和24/52周的5项哮喘控制问卷（ACQ-5）评分进行了评估。亚组分层基于基线血嗜酸性粒细胞≥150或≥300个细胞·μL-1或基线分数呼出的一氧化氮≥25 ppb和基线吸入皮质类固醇剂量。
结果：在所有2型哮喘亚组中，dupilumab与安慰剂相比，重度急性发作显著降低了54%至90%，在进入研究前急性发作次数更多的患者改善更大。同样，与安慰剂相比，所有亚组中都观察到FEV1（与安慰剂组比较的最小二乘法[LS]差异：≥1次急性发作组，0.15比0.25；≥2次急性发作组，0.12比0.32；≥3次急性发作组，0.09比0.38；多数p<0.05）和ACQ-5评分（LS平均差异范围：≥1次急性发作组，-0.30至-0.57；≥2次急性发作组，-0.29至-0.56；≥3次急性发作组，-0.43至-0.61；均p<0.05）的改善，与既往急性发作病史无关。
结论：在2型生物标志物升高的哮喘患者中，无论急性发作病史和基线ICS吸入剂量如何，dupilumab均能显著降低重度急性发作，改善FEV1和哮喘控制。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Eur Respir J. 2021 Jul 15;2004498. doi: 10.1183/13993003.04498-2020.)
(Eur Respir J. 2021 Jul 15;2004498. doi: 10.1183/13993003.04498-2020.)
Effect of exacerbation history on clinical response to dupilumab in moderate-severe uncontrolled asthma
Jonathan Corren, Constance H Katelaris, Mario Castro, Jorge F Maspero, Linda B Ford, David M G Halpin, Megan S Rice, Amr Radwan, Yamo Deniz, Paul Rowe, Ariel Teper, Michel Djandji
Abstract
BACKGROUND:The phase 3 QUEST study (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma has demonstrated the efficacy and safety of dupilumab 200 and 300 mg every 2 weeks versus placebo. This post hoc analysis assessed the effect of dupilumab on efficacy outcomes and asthma control across a range of historical exacerbation rates in patients with type 2-high asthma.
METHODS:Annualised severe exacerbation rates over the 52-week treatment period, pre-bronchodilator forced expiratory volume in 1 s (FEV1) at weeks 12/52, and the 5-item Asthma Control Questionnaire (ACQ-5) score at 24/52 were assessed in patients with ≥1, ≥2, or ≥3 exacerbations in the previous year. Subgroups were stratified by baseline blood eosinophils ≥150 or ≥300 cells·μL-1 or baseline fractional exhaled nitric oxide ≥25 ppb and baseline inhaled corticosteroid dose.
RESULTS:Across all type 2-high subgroups, dupilumab versus placebo significantly reduced severe exacerbations by 54 to 90%, with greater improvements in patients with more exacerbations prior to study initiation. Similarly, improvements in FEV1 (least squares [LS] difference versus placebo: ≥1 exacerbation, 0.15 to 0.25 L; ≥2 exacerbations, 0.12 to 0.32 L; ≥3 exacerbations, 0.09 to 0.38 L; majority p<0.05) and ACQ-5 score (LS mean difference range: ≥1 exacerbation, -0.30 to -0.57; ≥2 exacerbations, -0.29 to -0.56; ≥3 exacerbations, -0.43 to -0.61; all p<0.05) were observed, irrespective of prior exacerbation history, across all subgroups.
CONCLUSIONS:Dupilumab significantly reduced severe exacerbations and improved FEV1 and asthma control in patients with elevated type 2 biomarkers irrespective of exacerbation history and baseline ICS dose.
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