D3.422 - Dupilumab in children with multimorbid atopic phenotype: therapy efficacy, safety and biomarker changes

The development of biologicals that target key pathways of allergic inflammation has revolutionized the treatment of patients with moderate-to-severe, poorly controlled T2-inflammatory diseases. This study aimed to evaluate the efficacy and safety, time to response, and biomarker changes during dupilumab treatment in children with atopic multimorbidity

This study included 30 children (median age 9.4 [IQR 4.6–14.1] years), 63% male, with moderate-to-severe atopic dermatitis (AD) in the context of a multimorbid atopic phenotype. All patients had ≥ 2 confirmed allergic diseases, with the majority (80%) having ≥3 associated conditions, including allergic rhinitis, asthma, food allergy or eosinophilic esophagitis. All patients received dupilumab for at least 16 weeks. Efficacy and disease activity were assessed using standardized scales (SCORAD, EASI, CDLQI). Biomarker analysis included serum levels of TARC/CCL17, VEGF, DPP-4, periostin, blood eosinophils (Eos) and FeNO, measured at baseline and at week 16.

A rapid clinical response was observed: median SCORAD and EASI scores decreased 2-3-fold. By week 4, the majority (80%) achieved EASI50, and more than half (53%) achieved EASI75, EASI90 was observed in 20% patients. By week 16, significant improvement was confirmed: median SCORAD decreased from 54 to 12 (p<0.001), median EASI decreased from 18 to 2, CDLQI remarkably improved from 12 to 2 points (p=0.001). By week 16, the cumulative rate of EASI90 achievers increased to 70%. Among biomarkers, TARC/CCL17 levels significantly decreased by 72% (p<0.001) along with clinical improvement. Levels of VEGF and periostin showed a decreasing trend, while DPP-4 remained stable. Treatment also led to reduced airway inflammation (FeNO decreased from 23 to 15 ppb, p=0.046). Median Eos did not change significantly (p=0.643). Adverse events were rare (injection-site reactions in 17%), conjunctivitis was observed in 7% of patients. The frequency of acute respiratory infection episodes did not increase during treatment.

The study showed a unified picture of both the clinical and biomarker response to dupilumab in children forming a basis for personalized therapy and treatment efficacy prediction. Dupilumab demonstrated high clinical efficacy and a favorable safety profile in children with atopic multimorbidity. The biomarker TARC/CCL17 proved to be a sensitive indicator of treatment response.