Impact of asthma age of onset or duration on efficacy of dupilumab in moderate-to-severe type 2 asthma

Objective: Age of asthma onset is critical for determining heterogeneous asthma phenotypes. How onset and duration affect therapeutic response is not well understood. Phase 3 QUEST (NCT02414854) and open-label extension TRAVERSE (NCT02134028) studies demonstrated dupilumab’s efficacy up to three years in patients ≥12 years with uncontrolled, moderate-to-severe asthma. We assessed how age of asthma onset and asthma duration affect clinical efficacy of dupilumab in patients with moderate-to-severe type 2 inflammatory asthma. Methods: This post hoc analysis included patients with type 2 asthma from QUEST who enrolled in TRAVERSE. Annualized severe exacerbation rates (AER), change from parent study baseline (PSBL) in pre-bronchodilator forced expiratory volume in 1 s (FEV₁), and five-item Asthma Control Questionnaire (ACQ-5) score were assessed according to asthma age of onset (<18 years, 18–40 years, >40 years) and duration (<20 years, ≥20 years). Results: In all subgroups, treatment with dupilumab through QUEST and TRAVERSE progressively reduced AER (TRAVERSE Week 48–96 range, 0.160–0.333), increased pre-bronchodilator FEV₁ (TRAVERSE Week 96 change from PSBL range, 0.20–0.44 L), and reduced ACQ-5 scores (TRAVERSE Week 48 change from PSBL range, −1.63 to −1.84). In patients who received placebo during QUEST, treatment with dupilumab in TRAVERSE improved AER, FEV₁, and ACQ-5 in all subgroups. Conclusions: In patients with uncontrolled, moderate-to-severe type 2 asthma, treatment with dupilumab provides sustained, long-term exacerbation rate reductions and improvements in lung function and asthma control, across all subgroups, with higher reductions in AER and improvements in pre-bronchodilator FEV₁ seen in patients with later onset or longer duration.