Tezepelumab对未控制的严重哮喘的疗效：PATHWAY和NAVIGATOR临床试验的汇总分析
2023/07/25
摘要
背景：在2b期PATHWAY（评价MEDI9929[AMG 157]在未得到充分控制的重症哮喘成人受试者中的疗效和安全性的研究）和3期NAVIGATOR（评价Tezepelumab在未得到充分控制的重症哮喘成人和青少年受试者中的疗效和安全性的研究；NCT02054130）研究中显示，无论基线血嗜酸性粒细胞计数、FeNO水平及过敏状态如何，Tezepelumab均可减少重度未控制哮喘患者的病情加重。
目的：利用PATHWAY和NAVIGATOR的汇总数据，研究Tezepelumab在其他临床相关亚组中的疗效和安全性。
方法:PATHWAY和NAVIGATOR是设计相似的随机、双盲、安慰剂对照试验。本合并分析纳入了严重、未控制的哮喘患者（PATHWAY，18-75岁；NAVIGATOR，12-80岁），他们每4周皮下注射210毫克的Tezepelumab或安慰剂，共52周。计算了总体人群和根据炎症生物标志物水平或临床特征定义亚组的52周内哮喘年加重率与次要结局
结果：总计纳入了1334名患者（Tezepelumab，n = 665；安慰剂，n = 669）。与安慰剂相比，Tezepelumab使总体人群的哮喘年加重率降低了60%（比值比为0.40[95%置信区间为0.34-0.48]）。根据多种定义，在Tezepelumab治疗的高2型和低2型患者中均显著降低了哮喘患者病情加重。与安慰剂相比，Tezepelumab减少了哮喘患者病情加重相关的住院或急诊就诊次数，改善了总体和各亚组的次要结局。各治疗组的不良反应发生率相似。
结论：在临床相关亚组中，Tezepelumab可使严重、未控制的哮喘患者的病情加重率降低并改善其他预后，具有临床意义。本研究涉及的2项试验均已在www.clinicaltrials.gov（NCT02054130 [PATHWAY]、NCT03347279 [NAVIGATOR]）注册。
Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials
Corren, J., Menzies-Gow, A., Chupp, G., Israel, E., Korn, S., Cook, B., Ambrose, C. S., Hellqvist, Å., Roseti, S. L., Molfino, N. A., Llanos, J. P., Martin, N., Bowen, K., Griffiths, J. M., Parnes, J. R., & Colice, G.
ABSTRACT
BACKGROUND：Tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma across a range of baseline blood eosinophil counts and fractional exhaled nitric oxide levels, and irrespective of allergy status, in the phase 2b PATHWAY (Study to Evaluate the Efficacy and Safety of MEDI9929 [AMG 157] in Adult Subjects With Inadequately Controlled, Severe Asthma; NCT02054130) and phase 3 NAVIGATOR (Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma; NCT03347279) trials.
OBJECTIVE: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 trials 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 over 52 weeks and secondary outcomes were calculated in the overall population and in subgroups defined by inflammatory biomarker levels or clinical characteristics.
MEASUREMENTS AND MAIN RESULTS:Overall, 1,334 patients were included (tezepelumab, n = 665; placebo, n = 669). Tezepelumab reduced the annualized asthma exacerbation rate versus placebo by 60% (rate ratio, 0.40 [95% confidence interval, 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.
CONCLUSION:Tezepelumab resulted in clinically meaningful reductions in exacerbations and improvements in other outcomes in patients with severe, uncontrolled asthma, across clinically relevant subgroups. Clinical trials registered with www.clinicaltrials.gov (NCT02054130 [PATHWAY], NCT03347279 [NAVIGATOR]).
背景：在2b期PATHWAY（评价MEDI9929[AMG 157]在未得到充分控制的重症哮喘成人受试者中的疗效和安全性的研究）和3期NAVIGATOR（评价Tezepelumab在未得到充分控制的重症哮喘成人和青少年受试者中的疗效和安全性的研究；NCT02054130）研究中显示，无论基线血嗜酸性粒细胞计数、FeNO水平及过敏状态如何，Tezepelumab均可减少重度未控制哮喘患者的病情加重。
目的：利用PATHWAY和NAVIGATOR的汇总数据，研究Tezepelumab在其他临床相关亚组中的疗效和安全性。
方法:PATHWAY和NAVIGATOR是设计相似的随机、双盲、安慰剂对照试验。本合并分析纳入了严重、未控制的哮喘患者（PATHWAY，18-75岁；NAVIGATOR，12-80岁），他们每4周皮下注射210毫克的Tezepelumab或安慰剂，共52周。计算了总体人群和根据炎症生物标志物水平或临床特征定义亚组的52周内哮喘年加重率与次要结局
结果：总计纳入了1334名患者（Tezepelumab，n = 665；安慰剂，n = 669）。与安慰剂相比，Tezepelumab使总体人群的哮喘年加重率降低了60%（比值比为0.40[95%置信区间为0.34-0.48]）。根据多种定义，在Tezepelumab治疗的高2型和低2型患者中均显著降低了哮喘患者病情加重。与安慰剂相比，Tezepelumab减少了哮喘患者病情加重相关的住院或急诊就诊次数，改善了总体和各亚组的次要结局。各治疗组的不良反应发生率相似。
结论：在临床相关亚组中，Tezepelumab可使严重、未控制的哮喘患者的病情加重率降低并改善其他预后，具有临床意义。本研究涉及的2项试验均已在www.clinicaltrials.gov（NCT02054130 [PATHWAY]、NCT03347279 [NAVIGATOR]）注册。
(中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校)
(Am J Respir Crit Care Med. 2023 Jul 1; DOI: 10.1164/rccm.202210-2005OC)
(Am J Respir Crit Care Med. 2023 Jul 1; DOI: 10.1164/rccm.202210-2005OC)
Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials
Corren, J., Menzies-Gow, A., Chupp, G., Israel, E., Korn, S., Cook, B., Ambrose, C. S., Hellqvist, Å., Roseti, S. L., Molfino, N. A., Llanos, J. P., Martin, N., Bowen, K., Griffiths, J. M., Parnes, J. R., & Colice, G.
ABSTRACT
BACKGROUND：Tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma across a range of baseline blood eosinophil counts and fractional exhaled nitric oxide levels, and irrespective of allergy status, in the phase 2b PATHWAY (Study to Evaluate the Efficacy and Safety of MEDI9929 [AMG 157] in Adult Subjects With Inadequately Controlled, Severe Asthma; NCT02054130) and phase 3 NAVIGATOR (Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma; NCT03347279) trials.
OBJECTIVE: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 trials 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 over 52 weeks and secondary outcomes were calculated in the overall population and in subgroups defined by inflammatory biomarker levels or clinical characteristics.
MEASUREMENTS AND MAIN RESULTS:Overall, 1,334 patients were included (tezepelumab, n = 665; placebo, n = 669). Tezepelumab reduced the annualized asthma exacerbation rate versus placebo by 60% (rate ratio, 0.40 [95% confidence interval, 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.
CONCLUSION:Tezepelumab resulted in clinically meaningful reductions in exacerbations and improvements in other outcomes in patients with severe, uncontrolled asthma, across clinically relevant subgroups. Clinical trials registered with www.clinicaltrials.gov (NCT02054130 [PATHWAY], NCT03347279 [NAVIGATOR]).
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Mepolizumab治疗重症嗜酸性粒细胞性哮喘患者的长期疗效和安全性及其对小气道的影响
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重度哮喘的抗上皮来源细胞因子：系统评价和荟萃分析
