Monoclonal Antibody Improves Type 2 Inflammation Biomarkers in Children With Asthma

Decreases in type 2 inflammation biomarkers were similar in children with type 2 asthma who received dupilumab 100 mg (≤30 kg) or 200 mg (>30 kg) every 2 weeks in the phase 3 VOYAGE study, according to findings published in the Annals of Allergy, Asthma & Immunology. 

“Both dose regimens led to significant reductions in a broad range of biomarkers of type 2 inflammation, indicating that dupilumab effectively targets the underlying inflammatory pathways that contribute to asthma pathogenesis in children with moderate-to-severe type 2 asthma,” wrote Daniel J. Jackson, MD, of the University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, and coauthors.

The study investigated the pharmacokinetics of dupilumab and changes in type 2 biomarkers in children with uncontrolled, moderate-to-severe asthma who participated in VOYAGE. Over the 52 weeks of the VOYAGE trial, dupilumab reduced severe asthma exacerbations and improved lung function compared with placebo in children with evidence of type 2 inflammation.

The weight-tiered dupilumab dose regimens used in VOYAGE achieved dupilumab concentrations in children by week 12 that were within the therapeutic range for adults and adolescents, according to the study. Average steady-state dupilumab concentrations were 51.2 mg/L for dupilumab 100 mg and 79.4 mg/L for dupilumab 200 mg; the therapeutic range for adults and adolescents is considered 29 mg/L to 80 mg/L.

Reductions in type 2 biomarkers were greater in patients treated with dupilumab than in patients treated with placebo. Median percent changes between baseline and week 52 were in children treated with dupilumab 100 mg were -78.6% for serum total immunoglobulin E, -53.6% thymus- and activation-regulated chemokine, -25.7% for blood eosinophils, and -47.7% for fractional exhaled nitric oxide. With dupilumab 200 mg, median percent changes were  -78.6% for serum total immunoglobulin E, -43.7% for thymus- and activation-regulated chemokine, -33.3% for blood eosinophils, and -55.6% for fractional exhaled nitric oxide.

“Despite differences in exposure between the weight tiers, median decreases in type 2 biomarker levels were similar among patients,” researchers wrote. “Future longitudinal studies will determine whether these effects also translate to better long-term outcomes.”

Reference:
Jackson DJ, Bacharier LB, Phipatanakul W, et al. Dupilumab pharmacokinetics and effect on type 2 biomarkers in children with moderate-to-severe asthma. Ann Allergy Asthma Immunol. Published online March 21, 2023. doi: 10.1016/j.anai.2023.03.014