P4A041: Dupilumab Reduces Rescue Systemic Corticosteroid Use in Children with Uncontrolled Moderate-to-severe Asthma While Improving Lung Function, Regardless of Prior Exacerbation History

Background: .There is a need to decrease recurrent rescue systemic corticosteroid (SCS) exposure for the treatment of exacerbations in patients with asthma, especially children. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component of interleukin (IL) 4 and IL-13, key and central drivers of type 2 inflammation in multiple diseases. In VOYAGE (NCT02948959), dupilumab was generally well tolerated, significantly reduced severe asthma exacerbations, and improved lung function, in children with uncontrolled moderate-to-severe asthma.

Objective: This post hoc analysis of VOYAGE assessed dupilumab efficacy in reducing the need for rescue SCS in children aged 6–11 years with type 2 inflammation (baseline blood eosinophils ≥150 cells/µL or FeNO ≥20 ppb).

Methods: .Children aged 6–11 years were randomized to dupilumab 100/200mg or placebo, every 2 weeks for 52 weeks. The annualized rate of severe exacerbations, change from baseline in percent predicted (pp) FEV1, and annualized number of total SCS courses (including oral, IM, IV) were analysed in subgroups of patients stratified by number of exacerbations prior to VOYAGE.

Results: .The unadjusted annualized rate of severe exacerbations was 0.46 (placebo, n=43) vs 0.14 (dupilumab, n=77), 0.68 (placebo, n=31) vs 0.29 (dupilumab, n=69), and 0.99 (placebo, n=32) vs 0.68 (dupilumab, n=63), in patients with type 2 asthma with 1, 2 and ≥3 prior exacerbations, respectively. Mean (SD) change from baseline in ppFEV1 (%) at Week 12 in placebo vs dupilumab was 2.7 (10.6) vs 11.4 (15.4), 7.7 (12.8) vs 12.5 (18.5), and 3.3 (16.4) vs 9.7 (13.6), in patients with 1, 2 and ≥3 prior exacerbations, respectively. Unadjusted annualized total SCS courses in the placebo versus the dupilumab arm were 0.49 vs 0.16, 0.74 vs 0.33, and 1.18 vs 0.78, in patients with 1, 2 and ≥3 prior exacerbations, respectively.

Conclusion: .In children with uncontrolled moderate-to-severe asthma, dupilumab was effective in reducing SCS burden related to exacerbations while reducing exacerbation rates and improving lung function, regardless of prior exacerbation history.