Aim Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4/13, key and central drivers of type 2 (T2) inflammation. Dupilumab had an acceptable safety profile and showed clinical efficacy in children aged 6–11 years with uncontrolled moderate-to-severe asthma in the VOYAGE study (NCT02948959). This analysis aimed to assess dupilumab efficacy by inhaled corticosteroid (ICS) dose at baseline in children with T2 asthma in VOYAGE.

Material and Method Children received weight-based dupilumab 100/200 mg q2w or placebo in groups stratified by baseline medium- (n=198) or high- (n=152) ICS dose. In prespecified, multiplicity-controlled analyses, annualized severe exacerbation rate (AER) over the 52-week treatment period in the high-ICS group was evaluated. Other analyses were AER in the medium-ICS group and changes from baseline in pre-bronchodilator percent predicted forced expiratory volume in 1 second (ppFEV1) and fractional exhaled nitric oxide (FeNO) in both dose groups.

Results Baseline AERs in dupilumab/placebo recipients were 3.04/2.56 in the high-, and 2.28/1.88 in the medium-, ICS groups. Dupilumab vs placebo significantly reduced AER in the high- (63.3%; P=0.0004) and medium- (59.5%; P=0.0025) ICS groups. Least squares (LS) mean change from baseline in pre-bronchodilator ppFEV1 at Week 12 was significantly greater for dupilumab vs placebo in the medium-ICS group (LS mean difference 7.23 [3.20, 11.26]; P=0.0006) and numerically greater in the high-ICS group (2.64 [−2.22, 7.51]; P=0.2847). Baseline FeNO (dupilumab/placebo) was 34.08/28.02 and 30.47/28.67 for the high- and medium-ICS groups, respectively. By Week 12, FeNO was significantly reduced in both the high- (LS mean difference dupilumab vs placebo −21.05 [−26.47, −15.63]; P<0.0001) and medium-ICS groups (−15.43 [−19.31, −11.55]; P<0.0001).

Conclusions Dupilumab demonstrated clinical efficacy in children with uncontrolled T2 moderate-to-severe asthma, with significant reductions in AER and FeNO in both ICS groups, and significant/numeric improvements in ppFEV1 in the medium/high-dose ICS groups.