Dupilumab cuts exacerbations, improves lung function in paediatric asthma patients with high eosinophils

In the post hoc analysis of data from the phase III LIBERTY ASTHMA VOYAGE study, the monoclonal antibody dupilumab reduced exacerbations and improved lung function in children aged between 6 and 11 years with moderate-to-severe asthma and baseline blood eosinophil count of ≥500 cells/μL.

Compared with placebo recipients, participants in the dupilumab arm had significantly reduced adjusted annualized rate of severe exacerbations (0.249 vs 0.749; p<0.001), with a reduction of 67 percent (relative risk [RR], 0.33, 95 percent confidence interval [CI], 0.18–0.62).

Dupilumab was similarly favoured over placebo in subsets of children with blood eosinophil counts of ≥300 cells/μL (RR, 0.35, 95 percent CI, 0.22–0.56) and ≥150 cells/μL (RR, 0.39, 95 percent CI, 0.26–0.58). [PAS 2023, poster 1]

Dupilumab treatment also led to rapid and sustained improvements in pre-bronchodilator ppFEV₁^* in children with blood eosinophil count of ≥500 cells/μL. “The first significant timepoint was at week 2 (p<0.05),” said Dr Nicholas Jellots from Sanofi, Cambridge, Massachusetts, US, during the oral poster presentations at PAS 2023. The significance was sustained up until week 52 (p<0.01).

Compared with placebo, the least squares (LS) mean difference in pre-bronchodilator ppFEV₁ at week 12 in children with blood eosinophils ≥500 cells/μL was 6.47 (95 percent CI, 2.27–10.66). A similar trend favouring dupilumab over placebo was seen in the subgroups of children with blood eosinophil counts of ≥300 cells/μL (LS mean difference, 5.32, 95 percent CI, 1.76–8.88) and ≥150 cells/μL (LS mean difference, 4.98, 95 percent CI, 1.83–8.13).

High eosinophils = worse asthma control
“Children with moderate-to-severe asthma often remain asymptomatic despite standard-of-care treatments. [Moreover,] those with elevated eosinophil levels often experience more exacerbations and worse asthma control,” said Jellots.

As such, Jellots and his team sought to evaluate the efficacy of dupilumab in a subset of children with uncontrolled moderate-to-severe asthma and baseline blood eosinophil count of ≥500 cells/μL from the LIBERTY ASTHMA VOYAGE study.

The study comprised 174 children aged 6–11 years from the parent cohort of 408 children. Participants were randomized 2:1 to receive dupilumab 100/200 mg (by body weight tier at randomization) every 2 weeks or volume-matched placebo for 52 weeks. Mean age was 8.8 years in the dupilumab arm and 9.2 years in the placebo arm. More than two-thirds of the overall cohort were male.

Approximately half of the cohort had medium to high doses of inhaled corticosteroids at baseline. There were more participants in the dupilumab than the placebo arm who experienced ≥4 exacerbations in the prior year (29 percent vs 10 percent). Mean baseline eosinophil count was higher in the dupilumab vs the placebo arm (872.3 vs 817.5 cells/μL). Mean baseline fractional exhaled nitric oxide was similar between the experimental and the placebo arms (36.2 vs 35.5 ppb).

The current findings build on the initial LIBERTY ASTHMA VOYAGE results demonstrating the benefit of dupilumab in children with uncontrolled moderate-to-severe asthma. In this study, dupilumab provided better lung function and asthma control, with participants experiencing fewer asthma exacerbations than those receiving placebo. [N Engl J Med 2021;385:2230-2240]