Dupilumab Efficacy in Children With Uncontrolled, Moderate-to-Severe, Type 2 Asthma by Allergen Sensitization Level.

Abstract

Children with uncontrolled, moderate-to-severe asthma often have type 2 disease with allergic sensitization and/or elevated serum IgE. To examine dupilumab efficacy in children aged 6 to 11 years with/without allergen sensitization. In VOYAGE (NCT02948959), 408 children were randomized to receive dupilumab 100/200 mg every 2 weeks (by weight) or placebo for 52 weeks. This post hoc analysis included 336 children from VOYAGE with type 2 inflammation (eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb) and known baseline allergen sensitization status (based on total serum IgE and perennial allergen-specific IgE levels). The primary outcome assessed was annualized severe exacerbation rate; we also assessed change from baseline in pre- and postbronchodilator percent predicted forced expiratory volume in 1 second (ppFEV₁), Interviewer-Administered 7-Item Asthma Control Questionnaire (ACQ-7-IA) score, and total and allergen-specific IgE levels. Of 336 children with type 2 inflammation and known baseline allergen sensitization status, 75 (22%) were nonsensitized, 58 (17%) monoallergen sensitized, and 203 (60%) multiallergen sensitized. Dupilumab versus placebo reduced asthma exacerbations by 45%, 75%, and 60% in the non-, mono-, and multisensitized subgroups (P = .1286, .0376, and .0004), respectively, by week 52, with no apparent interaction between treatment group and sensitization status (P_int = .48). Similar improvements were observed across sensitization subgroups for pre- and postbronchodilator ppFEV₁, ACQ-7-IA, and total IgE levels. In children with type 2 asthma, dupilumab showed significant efficacy, reducing exacerbations and improving other outcomes in monoallergen- and multiallergen-sensitized patients, and numerical but nonsignificant effects in nonsensitized patients.