Dupilumab pharmacokinetics and effect on type 2 biomarkers in children with moderate-to-severe asthma.
Ann Allergy Asthma Immunol
; 131(1): 44-51.e4, 2023 07.
Article
in En
| MEDLINE
| ID: mdl-36958470
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Asthma
/
Antibodies, Monoclonal
Type of study:
Clinical_trials
Limits:
Adolescent
/
Adult
/
Child
/
Humans
Language:
En
Journal:
Ann Allergy Asthma Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2023
Type:
Article