PC3007: Dupilumab Efficacy in Children with Moderate-to-severe Type 2 Asthma Analyzed by High- or Medium-dose of Inhaled Corticosteroids at Baseline: LIBERTY ASTHMA VOYAGE Study

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4/-13, key and central drivers of type 2 inflammation in multiple diseases. Higher doses of ICS may be indicative of more severe asthma. In VOYAGE (NCT02948959), a 52-week randomized, double-blind, placebo-controlled study, dupilumab showed clinical efficacy with an acceptable safety profile in children aged 6–11 years with uncontrolled, moderate-to-severe asthma using medium or high-dose inhaled corticosteroids (ICS) and with evidence of type 2 inflammation (baseline blood eosinophils ≥150 cells/μL or baseline fractional exhaled nitric oxide [FeNO] ≥20 ppb) at baseline. This analysis evaluates dupilumab efficacy in this population stratified by medium or high dose ICS according to GINA 2015 criteria.

Methods: Children received weight-based dupilumab 100/200 mg every 2 weeks or placebo. 152 and 195 children received high- and medium-dose ICS at baseline (GINA 2015), respectively. In a prespecified, multiplicity-controlled analysis, annualized severe asthma exacerbation rates (AER) over the 52-week treatment period in the high-dose ICS group were evaluated. Other analyses were AER in the medium-dose ICS group and changes from baseline in pre-BD percent predicted (pp) FEV1 (%), and interviewer-administered 7-Item Asthma Control Questionnaire (ACQ-7-IA) score at Week 52 in both children with high- and medium-dose ICS at baseline.

Results: Baseline exacerbation rates in patients treated with dupilumab vs placebo were 3.04 (3.25) vs 2.56 (1.86) in the high-dose group, and 2.27 (1.86) vs 1.88 (1.19) in the medium-dose group, respectively. Dupilumab vs placebo significantly reduced AER by 63% (P=0.0004) in the high-, and by 59% (P=0.0028) in the medium-dose ICS groups. Pre-BD ppFEV1 at baseline (mean [SD]) in patients treated with dupilumab vs placebo were 77.93% (12.99) vs 75.80% (12.76) in the high-dose ICS group, and 77.27% (15.33) vs 80.36% (15.55) in the medium-dose ICS group, respectively. Least squares (LS) mean difference (95% CI) from baseline in pre-BD ppFEV1 at Week 52 was significantly greater with dupilumab vs placebo in both the high-dose ICS group (5.70 [0.99, 10.40]; P=0.0180) and the medium-dose ICS group (9.35 [4.38, 14.33]; P=0.0003). Baseline ACQ-7-IA scores (mean [SD]) in patients treated with dupilumab vs placebo were 2.17 (0.77) vs 2.08 (0.67) in the high-dose ICS group, and 2.14 (0.65) vs 2.14 (0.83) in the medium-dose ICS group, respectively. Reductions from baseline in ACQ-7-IA scores at Week 52 were significantly greater with dupilumab vs placebo in both the high-dose ICS group (−0.53 [−0.75, −0.31]; P< 0.0001) and the medium-dose ICS group (−0.40 [−0.60, −0.20]; P=0.0001).

Conclusion: Dupilumab demonstrated clinical efficacy in children with uncontrolled moderate-to-severe type 2 asthma regardless of ICS dose at baseline, with significant reductions in exacerbations, and significant improvements in both lung function and asthma control by end of treatment.