DUPILUMAB EFFICACY IN UNCONTROLLED, MODERATE-TO-SEVERE ALLERGIC ASTHMA IN THE PHASE 3 LIBERTY ASTHMA QUEST STUDY

Abstract

Introduction Dupilumab, a fully human interleukin (IL)-4 receptor-α monoclonal antibody inhibiting IL-4/IL-13 signaling pathways, key drivers of Type 2 inflammation, is approved for treating adults with inadequately controlled moderate-to-severe atopic dermatitis. In the phase 3 LIBERTY ASTHMA QUEST study (NCT02414854), dupilumab 200mg and 300mg administered every 2 weeks versus matched placebo reduced annualized severe exacerbation rates and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) and quality-of-life measures, and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma (≥12 years, without minimum baseline Type 2 inflammatory biomarkers). This post-hoc analysis assessed the efficacy of dupilumab in patients with and without allergic asthma. Methods Allergic asthma was defined as total serum IgE ≥30 kU/L and ≥1 positive perennial aeroallergen-specific IgE (≥0.35 kU/L) at baseline. Endpoints were annualized severe exacerbation rates over the 52-week treatment period and change from baseline to Week 12 in pre-bronchodilator FEV1 (L). Results 56% (n=1,066) of the intent-to-treat population met the criteria for allergic asthma. In patients with and without allergic asthma, dupilumab vs placebo significantly reduced annualized severe exacerbation rates during the treatment period (all P1 (L) at Week 12 (all PFigure). In both subgroups, improvements were greater with higher baseline blood eosinophil and FeNO levels. The most frequent adverse event in the dupilumab-treated groups versus placebo was injection-site reactions (15%/18% versus 5%/10%, respectively). Conclusions Add-on dupilumab reduced severe exacerbations and improved lung function in patients with allergic and non-allergic uncontrolled, moderate-to-severe asthma and was generally well tolerated. Figure. Change from baseline to Week 12 in pre-bronchodilator FEV1 (L) and annualized severe exacerbation rate during the 52-week treatment period in patients with and without allergic asthma and in subgroups defined by baseline blood-eosinophil counts and FeNO levels.