Dupilumab pharmacokinetics and effect on type 2 biomarkers in children with moderate-to-severe asthma

Abstract

Background: Type 2 inflammation is common in children with asthma. Dupilumab, a human antibody, blocks the signaling of interleukin -4 and -13, key and central drivers of type 2 inflammation. In the LIBERTY ASTHMA VOYAGE (NCT02948959) study, dupilumab reduced severe asthma exacerbations and improved lung function in children aged 6 to 11 years with uncontrolled, moderate-to-severe asthma. Objective: To assess the pharmacokinetics of dupilumab and type 2 biomarker changes in children with type 2 asthma in VOYAGE. Methods: Patients were randomized to dupilumab 100 mg (≤30 kg) or 200 mg (>30 kg) or placebo every 2 weeks for 52 weeks. Dupilumab concentrations and changes in type 2 biomarkers were assessed at each visit. Results: Dupilumab concentrations in serum reached a steady state by week 12, with mean concentrations of 51.2 mg/L and 79.4 mg/L in children receiving dupilumab 100 mg every 2 weeks and 200 mg every 2 weeks, respectively (therapeutic range in adults and adolescents: 29-80 mg/L). Reductions in type 2 biomarkers were comparable between regimens, and greater in patients treated with dupilumab vs placebo. In children treated with dupilumab 100 mg and 200 mg every 2 weeks, the median percent changes (Q1-Q3) from baseline at week 52 were, respectively, −78.6% (−86.3 to −69.80) and −78.6% (−84.9 to −70.1) for serum total immunoglobulin E, −53.6% (−66.4 to −34.6) and −43.7% (−58.6 to −28.5) for thymus and activation-regulated chemokine; −25.7% (−60.0 to 27.6) and −33.3% (−60.6 to 16.6) for blood eosinophils, and −47.7% (−73.8 to 18.9) and −55.6% (−73.6 to −20.0) for fractional exhaled nitric oxide. Conclusion: Weight-tiered dose regimens achieved mean concentrations within the dupilumab therapeutic range. The median decreases in type 2 biomarker levels were similar between dose regimens. Trial Registration: ClinicalTrials.gov Identifier: NCT02948959