Tezepelumab治疗重症、未控制哮喘的疗效：PATHWAY和NAVIGATOR研究的汇总分析
2023/04/21
摘要
背景：在PATHWAY (NCT02054130) 2b期和NAVIGATOR (NCT03347279) 3期研究中，Tezepelumab降低了重症、未控制哮喘患者的急性加重次数，且无论患者基线外周血嗜酸性粒细胞计数(BECs)、呼出气一氧化氮(fractional exhaled nitric oxide，FeNO)及过敏水平如何，都有降低作用。本研究利用PATHWAY和NAVIGATOR研究的汇总数据，旨在研究Tezepelumab在其他临床相关亚组中的有效性和安全性。
方法：PATHWAY和NAVIGATOR设计相似，均为随机、双盲、安慰剂对照研究。该荟萃分析包括接受每4周一次皮下注射Tezepelumab 210 mg或安慰剂治疗52周的重症、未控制哮喘患者（PATHWAY为18-75岁；NAVIGATOR为12-80岁）。在总体人群和由炎症生物标志物水平或临床特征定义的亚组中计算52周的哮喘急性加重率（AAER）和次要结局。
结果：本研究共纳入1,334名患者（Tezepelumab组，n = 665；安慰剂组，n = 669）。与安慰剂组相比，Tezepelumab降低了总体人群的AAER（比率比；95%置信区间）60%（0.40；0.34，0.48）。Tezepelumab可减少多种定义下的高T2和低T2患者急性加重率，均有临床意义。Tezepelumab还降低了急性加重相关的住院或急诊就诊次数，并改善了总体和亚组之间的次要结局。两组治疗的不良事件发生率相似。
结论：在全临床相关亚组中，Tezepelumab可在临床意义上减少重症、未控制哮喘患者急性加重，并改善其他结局。
Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of PATHWAY and NAVIGATOR Studies.
Corren J, Menzies-Gow A, Chupp G, Israel E, Korn S, Cook B, Ambrose CS, Hellqvist Å, Roseti SL, Molfino NA, Llanos JP, Martin N, Bowen K, Griffiths JM, Parnes JR, Colice G.
Abstract
BACKGROUND:Tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma across a range of baseline blood eosinophil counts (BECs) and fractional exhaled nitric oxide (FeNO) levels, and irrespective of allergy status, in the phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies. To examine the efficacy and safety of tezepelumab in additional clinically relevant subgroups using pooled data from PATHWAY and NAVIGATOR.
METHODS:PATHWAY and NAVIGATOR were randomized, double-blind, placebo-controlled studies with similar designs. This pooled analysis included patients with severe, uncontrolled asthma (PATHWAY, 18-75 years old; NAVIGATOR, 12-80 years old) who received tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. The annualized asthma exacerbation rate (AAER) over 52 weeks and secondary outcomes were calculated in the overall population and in subgroups defined by inflammatory biomarker levels or clinical characteristics.
RESULTS:Overall, 1,334 patients were included (tezepelumab, n=665; placebo, n=669). Tezepelumab reduced the AAER (rate ratios; 95% confidence intervals) versus placebo by 60% (0.40; 0.34, 0.48) in the overall population, and clinically meaningful reductions in exacerbations were observed in tezepelumab-treated patients with type 2-high and type 2-low disease by multiple definitions. Tezepelumab reduced exacerbation-related hospitalization or emergency department visits and improved secondary outcomes compared with placebo overall and across subgroups. The incidence of adverse events was similar between treatment groups.
CONCLUSIONS:Tezepelumab resulted in clinically meaningful reductions in exacerbations and improvements in other outcomes in patients with severe, uncontrolled asthma, across clinically relevant subgroups.
背景：在PATHWAY (NCT02054130) 2b期和NAVIGATOR (NCT03347279) 3期研究中，Tezepelumab降低了重症、未控制哮喘患者的急性加重次数，且无论患者基线外周血嗜酸性粒细胞计数(BECs)、呼出气一氧化氮(fractional exhaled nitric oxide，FeNO)及过敏水平如何，都有降低作用。本研究利用PATHWAY和NAVIGATOR研究的汇总数据，旨在研究Tezepelumab在其他临床相关亚组中的有效性和安全性。
方法：PATHWAY和NAVIGATOR设计相似，均为随机、双盲、安慰剂对照研究。该荟萃分析包括接受每4周一次皮下注射Tezepelumab 210 mg或安慰剂治疗52周的重症、未控制哮喘患者（PATHWAY为18-75岁；NAVIGATOR为12-80岁）。在总体人群和由炎症生物标志物水平或临床特征定义的亚组中计算52周的哮喘急性加重率（AAER）和次要结局。
结果：本研究共纳入1,334名患者（Tezepelumab组，n = 665；安慰剂组，n = 669）。与安慰剂组相比，Tezepelumab降低了总体人群的AAER（比率比；95%置信区间）60%（0.40；0.34，0.48）。Tezepelumab可减少多种定义下的高T2和低T2患者急性加重率，均有临床意义。Tezepelumab还降低了急性加重相关的住院或急诊就诊次数，并改善了总体和亚组之间的次要结局。两组治疗的不良事件发生率相似。
结论：在全临床相关亚组中，Tezepelumab可在临床意义上减少重症、未控制哮喘患者急性加重，并改善其他结局。
(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)
(Am J Respir Crit Care Med. 2023 Apr 4. doi: 10.1164/rccm.202210-2005OC.)
(Am J Respir Crit Care Med. 2023 Apr 4. doi: 10.1164/rccm.202210-2005OC.)
Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of PATHWAY and NAVIGATOR Studies.
Corren J, Menzies-Gow A, Chupp G, Israel E, Korn S, Cook B, Ambrose CS, Hellqvist Å, Roseti SL, Molfino NA, Llanos JP, Martin N, Bowen K, Griffiths JM, Parnes JR, Colice G.
Abstract
BACKGROUND:Tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma across a range of baseline blood eosinophil counts (BECs) and fractional exhaled nitric oxide (FeNO) levels, and irrespective of allergy status, in the phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies. To examine the efficacy and safety of tezepelumab in additional clinically relevant subgroups using pooled data from PATHWAY and NAVIGATOR.
METHODS:PATHWAY and NAVIGATOR were randomized, double-blind, placebo-controlled studies with similar designs. This pooled analysis included patients with severe, uncontrolled asthma (PATHWAY, 18-75 years old; NAVIGATOR, 12-80 years old) who received tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. The annualized asthma exacerbation rate (AAER) over 52 weeks and secondary outcomes were calculated in the overall population and in subgroups defined by inflammatory biomarker levels or clinical characteristics.
RESULTS:Overall, 1,334 patients were included (tezepelumab, n=665; placebo, n=669). Tezepelumab reduced the AAER (rate ratios; 95% confidence intervals) versus placebo by 60% (0.40; 0.34, 0.48) in the overall population, and clinically meaningful reductions in exacerbations were observed in tezepelumab-treated patients with type 2-high and type 2-low disease by multiple definitions. Tezepelumab reduced exacerbation-related hospitalization or emergency department visits and improved secondary outcomes compared with placebo overall and across subgroups. The incidence of adverse events was similar between treatment groups.
CONCLUSIONS:Tezepelumab resulted in clinically meaningful reductions in exacerbations and improvements in other outcomes in patients with severe, uncontrolled asthma, across clinically relevant subgroups.
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贝那利珠单抗治疗重症嗜酸性粒细胞性哮喘的最大真实世界有效性研究：ZEPHYR 2
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地塞米松与甲基强的松龙治疗重症哮喘：一个单中心、开放标签、平行组的临床试验
