Castro Mario, Rabe Klaus F, Corren Jonathan, Pavord Ian D, Katelaris Constance H, Tohda Yuji, Zhang Bingzhi, Rice Megan S, Maroni Jaman, Rowe Paul, Pirozzi Gianluca, Amin Nikhil, Ruddy Marcella, Akinlade Bolanle, Graham Neil M H, Teper Ariel
Washington University School of Medicine, St Louis, MO, USA.
LungenClinic Grosshansdorf and Christian Albrechts University, members of the German Center for Lung Research (DZL), Kiel, Germany.
ERJ Open Res. 2020 Jan 27;6(1). doi: 10.1183/23120541.00204-2019. eCollection 2020 Jan.
Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200 mg or 300 mg every 2 weeks reduced exacerbations and improved forced expiratory volume in 1 s (FEV) and quality of life over 52 weeks. This analysis evaluates dupilimab's effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers.
Patients were randomised to 52 weeks of subcutaneous dupilumab 200 mg every 2 weeks, 300 mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ≥150 eosinophils·µL, ≥300 eosinophils·µL, ≥25 ppb fractional exhaled nitric oxide ( ), and both ≥150 eosinophils·µL and ≥25 ppb , at baseline.
Dupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements placebo after 52 weeks in pre-bronchodilator FEV (0.20 and 0.13 L, respectively, placebo) and post-bronchodilator FEV (0.19 and 0.13 L, respectively), forced vital capacity (FVC) (0.20 and 0.14 L, respectively), forced expiratory flow (0.19 and 0.13 L·s, respectively) and pre-bronchodilator FEV/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference placebo in post-bronchodilator FEV slope of change (weeks 4-52) was significant (0.04 L·year; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or levels for most outcomes.
Dupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation.
度普利尤单抗是一种全人源单克隆抗体，可阻断白细胞介素-4和白细胞介素-13的共同受体成分，这两种细胞因子是2型炎症的关键驱动因素。在一项针对控制不佳的中重度哮喘患者的3期LIBERTY ASTHMA QUEST试验（NCT02414854）中，每2周添加200mg或300mg度普利尤单抗，在52周内可减少哮喘发作，并改善1秒用力呼气容积（FEV）和生活质量。本分析评估了度普利尤单抗对总体人群以及基线2型炎症生物标志物升高的亚组肺功能的影响。
患者被随机分配接受为期52周的皮下注射度普利尤单抗，每2周一次，剂量为200mg或300mg，或等量体积的安慰剂。对总体人群、基线时嗜酸性粒细胞≥150/μL、嗜酸性粒细胞≥300/μL、呼出一氧化氮分数（FeNO）≥25ppb以及嗜酸性粒细胞≥150/μL且FeNO≥25ppb的患者的肺功能结果进行分析。
度普利尤单抗治疗（每2周200mg和300mg）在52周后导致支气管扩张剂使用前FEV（分别比安慰剂增加0.20L和0.13L）、支气管扩张剂使用后FEV（分别增加0.19L和0.13L）、用力肺活量（FVC，分别增加0.20L和0.14L）、用力呼气流量（分别增加0.19L/s和0.13L/s）以及支气管扩张剂使用前FEV/FVC比值（分别增加1.75%和1.61%）在总体人群中显著改善（p<0.001）。支气管扩张剂使用后FEV变化斜率（第4 - 52周）与安慰剂相比差异显著（0.04L/年；p<0.05）。对于大多数结果，基线血嗜酸性粒细胞和/或FeNO水平升高的患者改善更大。
度普利尤单抗可改善控制不佳的中重度哮喘患者的肺功能结果，包括大气道和小气道测量以及固定性气道阻塞；特别是在2型炎症生物标志物升高的患者中。
