Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma. Issue 1 (27th January 2020)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: ERJ open research. Volume 6:Issue 1(2020)
• Publication Date: 2020-01-27
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; Respiration; Respiratory organs -- Diseases; Respiratory organs -- Diseases -- Treatment; Respiratory Tract Diseases; Electronic journals; Fulltext; Internet Resources; Periodicals; Periodical; 616.2005
• DOI: 10.1183/23120541.00204-2019
• Languages: English
• ISSNs: 2312-0541

Abstract

Background: 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 (FEV1 ) 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. Methods: 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 −1, ≥300 eosinophils·µL −1, ≥25 ppb fractional exhaled nitric oxide ( F eNO ), and both ≥150 eosinophils·µL −1 and ≥25 ppb F eNO, at baseline. Results: Dupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements versus placebo after 52 weeks in pre-bronchodilator FEV1 (0.20 and 0.13 L, respectively, versus placebo) and post-bronchodilator FEV1 (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 −1, respectively) and pre-bronchodilator FEV1 /FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV1 slope of change (weeks 4–52) was significant (0.04 L·year −1 ; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or F eNO levels for most outcomes. Conclusions: 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. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation, improving lung function outcomes in patients with uncontrolled, moderate-to-severe asthma http://bit.ly/2OhKMpi