Continuous Associations of Type 2 Biomarkers and Efficacy of Dupilumab in Children with Uncontrolled, Moderate-to-severe Asthma

Background: Dupilumab blocks the shared receptor component for IL-4/13, key and central drivers of type 2 inflammation. In VOYAGE, dupilumab vs placebo every 2 weeks for 52 weeks reduced severe asthma annualized exacerbation rate (AER), improved percent predicted pre-bronchodilator FEV1 (ppFEV1) and was generally well tolerated in children aged 6-11 years with uncontrolled, moderate-to-severe asthma. Aim: Evaluation of the predictive value of baseline blood eosinophil and FeNO levels as biomarkers for dupilumab response. Methods: The relationship between baseline type 2 biomarker (blood eosinophils alone, FeNO alone) and exacerbations and lung function were evaluated using penalized regression spline analyses in the dupilumab and placebo arms. Results: In the dupilumab group, the AER was low and was independent of baseline values of FeNO and blood eosinophils. Conversely, in the placebo group, both higher baseline FeNO and blood eosinophils were associated with a higher AER. In the dupilumab group, higher values of FeNO and blood eosinophils each were associated with a greater improvement in ppFEV1. In the placebo group, higher baseline eosinophil count (but not FeNO) was associated with smaller improvements in ppFEV1 (figure). Conclusions: Elevated FeNO or blood eosinophil count can identify children with uncontrolled moderate to severe asthma who are likely to respond to dupilumab.