Dupilumab Efficacy in Asthma Patients With FEV1 60–80% Predicted on Medium-Dose ICS: liberty asthma quest Study

Abstract

Background: Dupilumab (DPL), a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST study (NCT02414854), add-on DPL 200 or 300 mg every 2 weeks (q2w) vs matched placebo (PBO) reduced severe asthma exacerbations and improved pre-bronchodilator (BD) FEV1 in patients (pts) with uncontrolled, moderate-to-severe asthma. Treatment effects were greater with elevated levels of type 2 biomarkers at baseline (BL). Aim: To assess DPL efficacy in pts with moderate asthma defined as asthma pts with BL pre-BD FEV1 60–80% predicted (60–90% in adolescents), on medium-dose ICS and ≥1 controller, without a minimum requirement for BL blood eosinophil count or FeNO. Methods: Negative binomial models were used to analyze annualized severe asthma exacerbation rates during the 52-week treatment period and mixed-effects models with repeated measures were used to analyze change from BL in pre-BD FEV1 at Week 12. Results: 517/1,902 pts (27%) had pre-BD FEV1 60–80% predicted and were on medium-dose ICS at BL. In these pts, DPL 200/300mg q2w reduced annualized severe exacerbation rates by 44%/51% respectively vs PBO (P=0.06/P=0.01). DPL 200/300mg q2w vs PBO also improved FEV1 at Week 12 with a LS mean difference of 0.11L/0.09L, respectively (P=0.01/P=0.05). Overall, the most frequent adverse event in DPL 200/300mg vs PBO groups was injection-site reaction (15%/18% vs 5%/10%). Conclusion: Dupilumab meaningfully reduced severe exacerbations and improved FEV1 in moderate asthma pts with pre-BD FEV1 60–80% predicted and on medium-dose ICS, and was generally well tolerated.