Dupilumab plus medium-dose inhaled corticosteroid improves outcomes compared with placebo plus high-dose inhaled corticosteroid in pediatric patients with uncontrolled asthma

Purpose: The use of high-dose inhaled corticosteroids (ICS) in pediatric asthma raises concerns for systemic adverse effects such as growth suppression and adrenal axis effects, as well as local complications. Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation, reduced severe asthma exacerbations and improved lung function in children with uncontrolled asthma and type 2 inflammation in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). The objective of this post-hoc analysis from VOYAGE was to evaluate the potential advantages of dupilumab added on to medium-dose ICS compared with placebo plus high-dose ICS on clinical outcomes in children with asthma and type 2 inflammation.

Methods: In VOYAGE, children with moderate-to-severe asthma and type 2 inflammation (defined as baseline blood eosinophil count≥150 cells/μL or fractional exhaled nitric oxide≥20 ppb) received subcutaneous dupilumab 100/200 mg (by body weight≤30 kg/>30 kg) or placebo every 2 weeks for 52 weeks. We assessed adjusted annualized severe exacerbation rates, least squares (LS) mean difference from baseline in percent predicted pre-bronchodilator forced expiratory volume in 1 second (FEV1), and the proportion of patients achieving asthma control (7-item Asthma Control Questionnaire [ACQ-7] score<1.5) at Week 52 in the subgroup of patients who received dupilumab plus medium-dose ICS or placebo plus high-dose ICS.

Results: This analysis included 134 children given dupilumab plus medium-dose ICS and 50 given placebo plus high-dose ICS. At Week 52, dupilumab plus medium-dose ICS significantly reduced exacerbations compared with placebo plus high-dose ICS by 74%, with annualized severe exacerbation rates (95% CI) of 0.253 (0.157–0.405) vs 0.982 (0.622–1.552) and relative risk vs placebo (95% CI) of 0.257 (0.143–0.463); P<0.0001. Significant improvements in lung function were observed at Week 52 in children given dupilumab plus medium-dose ICS treatment, with LS mean difference in percent predicted pre-bronchodilator FEV1 vs placebo plus high-dose ICS of 10.47% (4.84–16.11); P=0.0003. At Week 52, greater proportions of children achieved well-controlled asthma in the dupilumab plus medium-dose ICS group vs the placebo plus high-dose ICS group, with 85.1% vs 72.0% achieving ACQ-7 score<1.5 (odds ratio vs placebo [95% CI]: 1.77 [0.75–4.15]; P=0.1930).

Conclusions: In children with moderate-to-severe asthma and type 2 inflammation, dupilumab plus medium-dose ICS reduced exacerbations and improved lung function and asthma control compared with placebo plus high-dose ICS.

Publication History

Article published online:
28 February 2025