重症哮喘患者2型生物标志物基线水平与对Tezepelumab反应性
2022/06/17
摘要
背景：Tezepelumab 是一种人单克隆抗体，可阻断胸腺基质淋巴细胞生成素（TSLP）的活性。在 IIb 期 PATHWAY 研究（NCT02054130）发现，与安慰剂相比，Tezepelumab可显著降低重症未控制哮喘成人的年化哮喘发作率（AAER）。本研究评估了Tezepelumab 在降低 PATHWAY 人群中 2 型（T2）炎症生物标志物水平方面的作用，以及T2 生物标志物基线水平与 AAER 之间的关系。
方法：成年重症未控制哮喘患者（n = 550）随机分为 Tezepelumab（每 4 周 70 毫克或 210 毫克，或每 2 周 280 毫克）治疗组和安慰剂治疗组，治疗周期52 周。在基线期和治疗52周分别测量外周血嗜酸性粒细胞计数、呼出气一氧化氮（FeNO）和血清总IgE、白介素 (IL)-5、IL-13、骨膜素、胸腺和活化调节趋化因子（TARC）及 TSLP。以基线生物标志物水平阈值（高/低）分析 AAER。
结果：基线期观察得知，T2炎症生物标志物（外周血嗜酸性粒细胞计数、FeNO、IL-5、IL-13 和骨膜素）之间呈正相关。治疗第 52 周，与安慰剂相比，Tezepelumab 210 mg 治疗组中所有生物标志物水平均较基线值下降。单独评估上述生物标志物时发现，无论基线期血嗜酸性粒细胞计数，FeNO ，或血清总 IgE、IL-5、IL-13、骨膜素、TARC 、TSLP水平如何，汇总 Tezepelumab 治疗队列与安慰剂治疗队列相比，哮喘急性发作减少了 55-83%。
结论：基线期观察得知，T2炎症特异性生物标志物之间存在正相关。Tezepelumab可降低多种 T2炎症生物标志物，即减轻气道炎症，且无论重症哮喘患者T2生物标志物谱基线水平如何，Tezepelumab均可减少其急性发作。
Baseline type 2 biomarker levels and response to tezepelumab in severe asthma
Corren J, Pham TH, Garcia Gil E, Sałapa K, Ren P, Parnes JR, Colice G, Griffiths JM.
Abstract
BACKGROUND：Tezepelumab is a human monoclonal antibody that blocks activity of thymic stromal lymphopoietin (TSLP). In the phase IIb PATHWAY study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo in adults with severe, uncontrolled asthma. We evaluated the effects of tezepelumab in reducing type 2 (T2) inflammatory biomarker levels in the PATHWAY population, and the relationship between baseline T2 biomarker levels and AAER.
METHODS：Adults with severe, uncontrolled asthma (n = 550) were randomized to tezepelumab (70 mg or 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. Blood eosinophil count, fractional exhaled nitric oxide (FeNO), and serum total immunoglobulin (Ig)E, interleukin (IL)-5, IL-13, periostin, thymus and activation-regulated chemokine (TARC), and TSLP were measured at baseline and over 52 weeks. AAERs were analyzed by baseline threshold (high/low) biomarker levels.
RESULTS：Positive correlations were observed between T2 inflammatory biomarkers (blood eosinophil count, FeNO, IL-5, IL-13 and periostin) at baseline. At Week 52, treatment with tezepelumab 210 mg reduced all biomarker levels measured from baseline versus placebo. Exacerbations were reduced by 55-83% in the pooled tezepelumab cohort versus placebo, irrespective of baseline blood eosinophil count, FeNO, or serum total IgE, IL-5, IL-13, periostin, TARC, or TSLP, when these biomarkers were assessed individually.
CONCLUSIONS：At baseline, positive correlations between specific T2 inflammatory biomarkers were observed. Tezepelumab reduced multiple T2 inflammatory biomarkers, which indicates decreased airway inflammation, and reduced exacerbations irrespective of baseline T2 biomarker profiles in patients with severe asthma.
背景：Tezepelumab 是一种人单克隆抗体，可阻断胸腺基质淋巴细胞生成素（TSLP）的活性。在 IIb 期 PATHWAY 研究（NCT02054130）发现，与安慰剂相比，Tezepelumab可显著降低重症未控制哮喘成人的年化哮喘发作率（AAER）。本研究评估了Tezepelumab 在降低 PATHWAY 人群中 2 型（T2）炎症生物标志物水平方面的作用，以及T2 生物标志物基线水平与 AAER 之间的关系。
方法：成年重症未控制哮喘患者（n = 550）随机分为 Tezepelumab（每 4 周 70 毫克或 210 毫克，或每 2 周 280 毫克）治疗组和安慰剂治疗组，治疗周期52 周。在基线期和治疗52周分别测量外周血嗜酸性粒细胞计数、呼出气一氧化氮（FeNO）和血清总IgE、白介素 (IL)-5、IL-13、骨膜素、胸腺和活化调节趋化因子（TARC）及 TSLP。以基线生物标志物水平阈值（高/低）分析 AAER。
结果：基线期观察得知，T2炎症生物标志物（外周血嗜酸性粒细胞计数、FeNO、IL-5、IL-13 和骨膜素）之间呈正相关。治疗第 52 周，与安慰剂相比，Tezepelumab 210 mg 治疗组中所有生物标志物水平均较基线值下降。单独评估上述生物标志物时发现，无论基线期血嗜酸性粒细胞计数，FeNO ，或血清总 IgE、IL-5、IL-13、骨膜素、TARC 、TSLP水平如何，汇总 Tezepelumab 治疗队列与安慰剂治疗队列相比，哮喘急性发作减少了 55-83%。
结论：基线期观察得知，T2炎症特异性生物标志物之间存在正相关。Tezepelumab可降低多种 T2炎症生物标志物，即减轻气道炎症，且无论重症哮喘患者T2生物标志物谱基线水平如何，Tezepelumab均可减少其急性发作。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(Allergy. 2022 Jun;77(6):1786-1796. doi: 10.1111/all.15197.)
(Allergy. 2022 Jun;77(6):1786-1796. doi: 10.1111/all.15197.)
Baseline type 2 biomarker levels and response to tezepelumab in severe asthma
Corren J, Pham TH, Garcia Gil E, Sałapa K, Ren P, Parnes JR, Colice G, Griffiths JM.
Abstract
BACKGROUND：Tezepelumab is a human monoclonal antibody that blocks activity of thymic stromal lymphopoietin (TSLP). In the phase IIb PATHWAY study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo in adults with severe, uncontrolled asthma. We evaluated the effects of tezepelumab in reducing type 2 (T2) inflammatory biomarker levels in the PATHWAY population, and the relationship between baseline T2 biomarker levels and AAER.
METHODS：Adults with severe, uncontrolled asthma (n = 550) were randomized to tezepelumab (70 mg or 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. Blood eosinophil count, fractional exhaled nitric oxide (FeNO), and serum total immunoglobulin (Ig)E, interleukin (IL)-5, IL-13, periostin, thymus and activation-regulated chemokine (TARC), and TSLP were measured at baseline and over 52 weeks. AAERs were analyzed by baseline threshold (high/low) biomarker levels.
RESULTS：Positive correlations were observed between T2 inflammatory biomarkers (blood eosinophil count, FeNO, IL-5, IL-13 and periostin) at baseline. At Week 52, treatment with tezepelumab 210 mg reduced all biomarker levels measured from baseline versus placebo. Exacerbations were reduced by 55-83% in the pooled tezepelumab cohort versus placebo, irrespective of baseline blood eosinophil count, FeNO, or serum total IgE, IL-5, IL-13, periostin, TARC, or TSLP, when these biomarkers were assessed individually.
CONCLUSIONS：At baseline, positive correlations between specific T2 inflammatory biomarkers were observed. Tezepelumab reduced multiple T2 inflammatory biomarkers, which indicates decreased airway inflammation, and reduced exacerbations irrespective of baseline T2 biomarker profiles in patients with severe asthma.
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