Laboratory Safety of Dupilumab Treatment in Children with Atopic Dermatitis Aged 6 Months to 6 Years
Previous clinical studies in children aged 6–12 years with moderate-to-severe atopic dermatitis have demonstrated laboratory safety during dupilumab treatment. The randomized study presented below supplements the data for the age group from 6 months to 6 years.
Study Methodology and Population
A total of 161 children from Europe and North America aged 6 months to 6 years with moderate-to-severe atopic dermatitis, who had not achieved disease control with topical therapy, were included in a randomized, placebo-controlled, double-blind phase III study. They were randomized in a 1:1 ratio and treated for 16 weeks with dupilumab (a human monoclonal antibody inhibiting the signaling pathways of interleukin-4 and -13) administered subcutaneously every 4 weeks (at a dose of 200 mg for those weighing 5-15 kg or 300 mg for those weighing 15-30 kg) plus topical corticosteroids (TCS; 1% hydrocortisone acetate in cream form; n = 83; mean age 4.2 years) or placebo plus TCS (n = 79; mean age 3.8 years).
Peripheral blood (hematology and biochemistry) and urine samples were analyzed before entering the study and subsequently after 4 and 16 weeks of treatment. Exclusion criteria for laboratory values at study entry were as follows:
- Thrombocytopenia ≤ 100 × 109/l
- Neutropenia ≤ 1.0 × 109/l in patients under 1 year of age and ≤ 1.5 × 109/l in patients aged 1 to 6 years
- Eosinophilia > 5000/µl
- Creatine kinase > 2.5 times the upper limit of normal
- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 3 times the upper limit of normal
Results
The mean eosinophil level at study entry was 1.09 (standard deviation [SD] 0.73) × 109/l in patients treated with dupilumab and 1.10 (SD 0.74) × 109/l in the placebo group. After 4 and 16 weeks, this increased compared to baseline and reference values in patients treated with dupilumab, with an average change of 0.31 (SD 1.37) × 109/l at week 16. The average change in the placebo group was –0.18 (SD 0.75) × 109/l. The increased eosinophil level was not associated with clinical symptoms; in 2 patients treated with dupilumab, it was evaluated as an adverse event but did not require treatment discontinuation.
The mean platelet level was above the reference range at study entry and after 4 and 16 weeks of treatment in both groups. In the dupilumab-treated group, a slight decrease in platelet levels was observed after 4 and 16 weeks of treatment compared to baseline values, with an average decrease of –0.16 × 109/l after 16 weeks. The average change in the placebo group was 17 × 109/l.
During the 16 weeks of treatment, no significant differences were observed in the mean levels of leukocytes, neutrophils, or hemoglobin. One case of increased leukocyte count and one case of neutropenia were reported in the dupilumab-treated group, which were evaluated as adverse events but were not associated with clinical symptoms and did not require treatment discontinuation.
In both groups, a slight increase in alkaline phosphatase (ALP) levels was observed (within reference values, with a numerically higher increase in the dupilumab group) and a decrease in ALT and lactate dehydrogenase (LDH) levels (both more significant in the dupilumab-treated group).
No clinically significant changes were observed in metabolic parameters, electrolyte levels, renal and liver parameters, and lipidogram during treatment.
Conclusion
No significant changes in laboratory parameters were observed in children aged 6 months to 6 years with moderate-to-severe atopic dermatitis during dupilumab treatment. The results are similar to those in children aged 6–12 years and indicate that routine laboratory monitoring is not necessary during treatment. Adverse events were infrequent, were not associated with clinical symptoms, and did not require treatment discontinuation. However, the study is limited by the small number of participants and the exclusion of patients with laboratory abnormalities.
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Source: Paller A. S., Siegfried E. C., Cork M. J. et al. Laboratory safety from a randomized 16-week phase III study of dupilumab in children aged 6 months to 5 years with moderate-to-severe atopic dermatitis. Paediatr Drugs 2023; 25 (1): 67–77, doi: 10.1007/s40272-022-00553-8.
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