Dupilumab efficacy in subgroups of type 2 asthma with high-dose inhaled corticosteroids at baseline
Arnaud Bourdin, J. Christian Virchow, Alberto Papi, Njira Lugogo, Philip G. Bardin, Martti Antila, David Halpin, Nadia Daizadeh, Michel Djandji, Benjamin Ortiz, Juby A. Jacob‐Nara, Rebecca Gall, Yamo Deniz, Paul J. Rowe
Abstract
Background and objective Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13, key and central drivers of type 2 inflammation in multiple diseases. In phase 3 QUEST (NCT02414854), add-on dupilumab 200 and 300 mg every 2 weeks reduced severe exacerbations, improved pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ), and was generally well tolerated in patients with uncontrolled moderate-to-severe asthma. This post hoc analysis assessed dupilumab efficacy in subpopulations of patients with type 2 asthma and high-dose inhaled corticosteroids (ICS). Methods Adjusted annualized severe exacerbation rates over the treatment period, least squares (LS) mean change from baseline at Week 12 in pre-bronchodilator FEV 1 , and LS mean change from baseline at Week 24 in 5-item Asthma Control Questionnaire (ACQ-5) scores were analyzed in subgroups of patients receiving high-dose (>500 μg) ICS with baseline blood eosinophils ≥150 cells/μL and/or fractional exhaled nitric oxide ≥25 ppb. Subgroups included allergic phenotype (with/without), comorbid chronic rhinosinusitis and/or nasal polyposis (with/without), pre-bronchodilator FEV 1 /forced vital capacity (<70%/≥70%), blood eosinophil level, exacerbation history, median baseline pre-bronchodilator FEV 1 , age at asthma onset (≤40/>40 years), median FEV 1 reversibility, body mass index (<30/≥30 kg/m 2 ), and sex. Results Dupilumab vs placebo reduced exacerbations and improved pre-bronchodilator FEV 1 at Week 12 and ACQ-5 at Week 24 across subgroups of patients with type 2 asthma and high-dose ICS at baseline. Dupilumab was also effective in patients receiving medium-dose ICS. Conclusion Dupilumab reduced severe exacerbations and improved lung function and asthma control in subgroups of patients with type 2 asthma and high-dose ICS at baseline. Clinical trial registration number NCT02414854.