Dupilumab在不可控制的中度至重度过敏性哮喘患者的疗效研究
2020/10/14
摘要
背景：IL-4和IL-13是2型炎症（包括IgE介导的过敏性哮喘炎症）的关键驱动因素，而Dupilumab可以阻断IL-4和IL-13的共享受体部分。在LIBERTY ASTHMA QUEST（NCT02414854）研究中，患有不受控制的中度至重度哮喘患者使用了dupilumab后，第一秒用力呼气容积（FEV1）得到了提高，并且重度哮喘的加重得到减少。在基线水平2型炎症生物标记物（血液中的嗜酸性粒细胞和呼出的一氧化氮分数）提高的患者中，dupilumab的效果更加有效。
目的：我们评估了dupilumab对有或没有过敏性哮喘证据（在基线时血清总IgE≥30IU/mL和≥1常年性气变应原特异性IgE≥0.35kU/L）的QUEST患者中哮喘关键结局的影响。
方法：评估52周治疗期间严重恶化率以及FEV1，哮喘控制和2型炎症标志物自基线的变化。
结果：在过敏性哮喘亚组（n = 1083）中，与安慰剂相比，dupilumab每2周注射200/300 mg，在第十二周降低了重度哮喘急性发作率（L36.9％/ L45.5％；均P <.01），FEV1也得到改善。（0.13 L / 0.16 L；均P <0.001；在第2周的首次评估中明显改善），而在基线时2型炎症生物标志物升高的患者中观察到更大的疗效和更佳的哮喘控制。 Dupilumab治疗还使2型炎症生物标记物得到持续快速减少。在没有过敏性哮喘证据的患者中也观察到相似的结果（n=819）。
结论：在有或没有过敏性哮喘证据的不受控制的中重度哮喘患者中，Dupilumab降低了严重恶化率，改善了FEV1和哮喘控制并抑制了2型炎症生物标志物。这也进一步突出了IL-4和IL- 13在气道炎症中的重要作用。
Dupilumab Efficacy in Patients with Uncontrolled, Moderate-to-Severe Allergic Asthma
Jonathan Corren MD, Mario Castro MD.
Abstract
BACKGROUND:Dupilumab blocks the shared receptor component for IL-4 and IL-13, key drivers of type 2 inflammation, including IgE-mediated allergic inflammation in asthma. In the LIBERTY ASTHMA QUEST (NCT02414854) study, dupilumab reduced severe asthma exacerbations and improved forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers (blood eosinophils and fractional exhaled nitric oxide) at baseline.
OBJECTIVE:We assessed dupilumab’s effect on key asthma outcomes in QUEST patients with/without evidence of allergic asthma (total serum IgE≥30IU/mL and ≥1perennial aeroallergen-specific IgE≥0.35 kU/L at baseline).
METHODS:Severe exacerbation rates and change from baseline in FEV1, asthma control, and markers of type 2 inflammation during the 52-week treatment period were assessed.
RESULTS:In the allergic asthma subgroup (n=1083), dupilumab 200/300mg every 2 weeks versus placebo reduced severe asthma exacerbation rates (-36.9%/-45.5%; both P < .01), improved FEV1 at week 12 (0.13L/0.16L; both P<.001; improvements were evident by the first evaluation at week 2) with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers at baseline, and improved asthma control. Dupilumab treatment also resulted in rapid and sustained reductions in type 2 inflammatory biomarkers. Comparable results were observed in patients without evidence of allergic asthma (n=819).
CONCLUSION:Dupilumab reduced severe exacerbation rates, improved FEV1 and asthma control, and suppressed type 2 inflammatory biomarkers in patients with uncontrolled,moderate-to-severe asthma with or without evidence of allergic asthma, highlighting the key role of IL-4 and IL-13 in airway inflammation.
背景：IL-4和IL-13是2型炎症（包括IgE介导的过敏性哮喘炎症）的关键驱动因素，而Dupilumab可以阻断IL-4和IL-13的共享受体部分。在LIBERTY ASTHMA QUEST（NCT02414854）研究中，患有不受控制的中度至重度哮喘患者使用了dupilumab后，第一秒用力呼气容积（FEV1）得到了提高，并且重度哮喘的加重得到减少。在基线水平2型炎症生物标记物（血液中的嗜酸性粒细胞和呼出的一氧化氮分数）提高的患者中，dupilumab的效果更加有效。
目的：我们评估了dupilumab对有或没有过敏性哮喘证据（在基线时血清总IgE≥30IU/mL和≥1常年性气变应原特异性IgE≥0.35kU/L）的QUEST患者中哮喘关键结局的影响。
方法：评估52周治疗期间严重恶化率以及FEV1，哮喘控制和2型炎症标志物自基线的变化。
结果：在过敏性哮喘亚组（n = 1083）中，与安慰剂相比，dupilumab每2周注射200/300 mg，在第十二周降低了重度哮喘急性发作率（L36.9％/ L45.5％；均P <.01），FEV1也得到改善。（0.13 L / 0.16 L；均P <0.001；在第2周的首次评估中明显改善），而在基线时2型炎症生物标志物升高的患者中观察到更大的疗效和更佳的哮喘控制。 Dupilumab治疗还使2型炎症生物标记物得到持续快速减少。在没有过敏性哮喘证据的患者中也观察到相似的结果（n=819）。
结论：在有或没有过敏性哮喘证据的不受控制的中重度哮喘患者中，Dupilumab降低了严重恶化率，改善了FEV1和哮喘控制并抑制了2型炎症生物标志物。这也进一步突出了IL-4和IL- 13在气道炎症中的重要作用。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（J Allergy Clin Immunol Pract. 2020 Feb;8(2):516-526）
（J Allergy Clin Immunol Pract. 2020 Feb;8(2):516-526）
Dupilumab Efficacy in Patients with Uncontrolled, Moderate-to-Severe Allergic Asthma
Jonathan Corren MD, Mario Castro MD.
Abstract
BACKGROUND:Dupilumab blocks the shared receptor component for IL-4 and IL-13, key drivers of type 2 inflammation, including IgE-mediated allergic inflammation in asthma. In the LIBERTY ASTHMA QUEST (NCT02414854) study, dupilumab reduced severe asthma exacerbations and improved forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers (blood eosinophils and fractional exhaled nitric oxide) at baseline.
OBJECTIVE:We assessed dupilumab’s effect on key asthma outcomes in QUEST patients with/without evidence of allergic asthma (total serum IgE≥30IU/mL and ≥1perennial aeroallergen-specific IgE≥0.35 kU/L at baseline).
METHODS:Severe exacerbation rates and change from baseline in FEV1, asthma control, and markers of type 2 inflammation during the 52-week treatment period were assessed.
RESULTS:In the allergic asthma subgroup (n=1083), dupilumab 200/300mg every 2 weeks versus placebo reduced severe asthma exacerbation rates (-36.9%/-45.5%; both P < .01), improved FEV1 at week 12 (0.13L/0.16L; both P<.001; improvements were evident by the first evaluation at week 2) with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers at baseline, and improved asthma control. Dupilumab treatment also resulted in rapid and sustained reductions in type 2 inflammatory biomarkers. Comparable results were observed in patients without evidence of allergic asthma (n=819).
CONCLUSION:Dupilumab reduced severe exacerbation rates, improved FEV1 and asthma control, and suppressed type 2 inflammatory biomarkers in patients with uncontrolled,moderate-to-severe asthma with or without evidence of allergic asthma, highlighting the key role of IL-4 and IL-13 in airway inflammation.
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