Weight-tiered dose regimens of dupilumab may affect type 2 biomarkers

Key takeaways:

• Weight-tiered regimens kept mean dupilumab concentrations within therapeutic range.
• Dose regimens yielded similar median decreases in type 2 biomarker levels.

Weight-tiered dose regimens of dupilumab affected type 2 biomarkers and kept dupilumab concentrations in a therapeutic range in children with moderate to severe asthma, according to a study.

“In our analysis of pharmacokinetics in children aged 6 to 11 years with moderate to severe asthma, dupilumab concentrations in serum reached steady state at week 12 for both the 100 mg and 200 mg [every 2 weeks] weight-tiered dupilumab dosing regimens,” Daniel J. Jackson, MD, from the University of Wisconsin School of Medicine and Public Health, and colleagues wrote in Annals of Allergy, Asthma & Immunology. “The weight-tiered dupilumab regimens were selected to normalize dupilumab exposure to achieve exposure in the therapeutic range that was observed in adults and adolescents.”

In a study of 408 children aged 6 to 11 years with uncontrolled moderate to severe asthma, participants were randomly assigned to receive dupilumab (body weight: 30 kg, 100 mg; > 30 kg, 200 mg) or matched placebo.

Eighty-six percent of the participants met the definition for type 2 inflammatory asthma, and of those 350 participants, 236 were in the dupilumab group and 114 were in the placebo group. Of the participants with blood eosinophils measuring 300 cells per µL or greater, 175were in the dupilumab group and 84 were in the placebo group.

Researchers analyzed changes in type 2 biomarker levels, including serum total IgE, serum thymus and activation-regulated chemokine (TARC), blood eosinophil counts, and fractional exhaled nitric oxide, at each visit throughout a 52-week treatment period.

The researchers found that children receiving dupilumab at 100 mg showed lower mean serum concentrations than those receiving 200 mg throughout the entire treatment period.

Dupilumab reduced serum total IgE throughout the treatment period by a median of 78.6% in both regimens. Patients receiving the placebo experienced a small increase in serum total IgE of approximately 4% to 5.7%.

The dupilumab groups experienced significantly reduced median serum TARC levels compared with the placebo group regardless of dose regimen.

While decreases in median blood eosinophil levels were similar between the placebo and the dupilumab 100 mg groups, there was a significantly greater decrease in the dupilumab 200 mg group.

Dupilumab median FeNO levels were reduced by 46.4% in the dupilumab 100 mg group and 55.7% in the dupilumab 200 mg group by week 2.

“The weight-tiered dose regimens that were selected to normalize dupilumab exposure achieved serum dupilumab concentrations within the therapeutic range,” Jackson and colleagues wrote. “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.”