tezepelumab对重度哮喘和持续性气流受限患者的疗效。
Efficacy of tezepelumab in patients with severe asthma and persistent airflow obstruction.
作者信息
Israel Elliot, Castro Mario, Ambrose Christopher S, Llanos Jean-Pierre, Molfino Nestor A, Martin Nicole L, Ponnarambil Sandhia S, Martin Neil
机构信息
Pulmonary and Critical Care Medicine, Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, KS, USA.
出版信息
ERJ Open Res. 2024 Nov 25;10(6). doi: 10.1183/23120541.00164-2024. eCollection 2024 Nov.
BACKGROUND
Persistent airflow obstruction (PAO) in patients with asthma can be difficult to treat. Tezepelumab blocks thymic stromal lymphopoietin, an epithelial cytokine implicated in asthma pathogenesis. This analysis evaluated the efficacy of tezepelumab in patients with severe, uncontrolled asthma and PAO.
METHODS
PATHWAY (phase 2b) and NAVIGATOR (phase 3) were multicentre, randomised, double-blind, placebo-controlled studies. This analysis included PATHWAY and NAVIGATOR patients who received tezepelumab 210 mg or placebo every 4 weeks for 52 weeks. Change from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 s (FEV) and the annualised asthma exacerbation rate (AAER) over 52 weeks were assessed in patients with and without PAO (post-bronchodilator FEV/forced vital capacity ratio <0.7) at baseline.
RESULTS
Of the 1334 included patients, 782 (58.6%) had PAO at baseline. At week 52, greater improvements in pre-bronchodilator FEV from baseline were observed in tezepelumab placebo recipients with PAO (least-squares (LS) mean 0.24 0.07 L; difference 0.17 L, 95% confidence interval (CI): 0.11-0.23) and without PAO (LS mean 0.20 0.12 L; difference 0.08 L, 95% CI: 0.01-0.15). Tezepelumab reduced the AAER placebo by 61% (95% CI: 51-69) and 56% (95% CI: 42-67) in patients with and without PAO, respectively. For patients with PAO at baseline, the proportion without PAO at week 52 was higher with tezepelumab (12.1%) than placebo (6.6%) (odds ratio 1.96, 95% CI: 1.30-2.94).
CONCLUSION
Tezepelumab improved lung function and reduced exacerbations placebo in patients with severe, uncontrolled asthma with and without PAO.
背景
哮喘患者的持续性气流受限（PAO）可能难以治疗。tezepelumab可阻断胸腺基质淋巴细胞生成素，这是一种与哮喘发病机制有关的上皮细胞因子。本分析评估了tezepelumab在重度、未控制的哮喘和PAO患者中的疗效。
方法
PATHWAY（2b期）和NAVIGATOR（3期）是多中心、随机、双盲、安慰剂对照研究。本分析纳入了PATHWAY和NAVIGATOR研究中接受tezepelumab 210mg或安慰剂，每4周一次，共52周的患者。在基线时存在和不存在PAO（支气管扩张剂后1秒用力呼气容积/用力肺活量比值<0.7）的患者中，评估从基线到第52周支气管扩张剂前1秒用力呼气容积（FEV）的变化以及52周内的年化哮喘急性加重率（AAER）。
结果
在纳入的1334例患者中，782例（58.6%）在基线时存在PAO。在第52周时，在基线时存在PAO的tezepelumab治疗组患者中，支气管扩张剂前FEV较基线有更大改善（最小二乘法（LS）均值0.24±0.07L；差值0.17L，95%置信区间（CI）：0.11 - 0.23），在不存在PAO的患者中也是如此（LS均值0.20±0.12L；差值0.08L，95%CI：0.01 - 0.15）。Tezepelumab使存在PAO和不存在PAO的患者的AAER较安慰剂分别降低了61%（95%CI：51 - 69）和56%（95%CI：42 - 67）。对于基线时存在PAO的患者，在第52周时不存在PAO的比例在tezepelumab组（12.1%）高于安慰剂组（6.6%）（优势比1.96，95%CI：1.30 - 2.94）。
结论
Tezepelumab在伴有和不伴有PAO的重度、未控制哮喘患者中，与安慰剂相比，改善了肺功能并减少了急性加重。
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