MOLECULAR MECHANISMS AND CLINICAL EFFICACY OF TARGETED THERAPY FOR ATOPIC DERMATITIS IN ADOLESCENTS

Abstract

Atopic dermatitis in adolescents is associated with epidermal barrier dysfunction and activation of immune-inflammatory signaling pathways, which explains the growing interest in targeted therapy; the aim of the study was to assess its molecular basis and clinical efficacy in patients aged 12–17 years with moderate to severe atopic dermatitis. A randomized, double-blind, placebo-controlled phase III study was conducted at the Children’s City Clinical Hospital in Krasnodar. The study included 10 adolescents with a body weight of ≥40 kg and a confirmed diagnosis of atopic dermatitis: 6 girls and 4 boys. The patients were divided into three groups: 15 mg of the drug — 4 patients, 30 mg of the drug — 3 patients, and placebo — 3 patients. The duration of therapy was 16 weeks. The primary endpoints were achievement of EASI-75 and vIGA-AD 0/1. Secondary endpoints included EASI-90, a reduction in itch intensity by at least 4 points on the WP-NRS, changes in quality of life according to DLQI and CDLQI, sleep parameters according to ADerm-IS, and anxiety and depression scores according to HADS-A and HADS-D. Safety was assessed by the frequency of adverse events, serious adverse events, and laboratory abnormalities. Statistical analysis was performed using MedCalc v.20.1; differences were considered statistically significant at p<0.05. By week 16, adolescents receiving targeted therapy showed a more pronounced reduction in inflammatory disease activity compared with the placebo group. EASI-75 was achieved in 70–75% of patients in the active treatment groups versus 30% in the placebo group, while vIGA-AD 0/1 was achieved in 63–67% versus 25%, respectively. Improvements were also observed in EASI-90, itch intensity, sleep quality, and quality of life. The need for rescue therapy was higher among patients receiving placebo and lower in the active treatment groups. The most common adverse events were acne, headache, upper respiratory tract infections, nasopharyngitis, and transient elevation of creatine phosphokinase. Serious adverse events were rare. Targeted therapy in adolescents with moderate to severe atopic dermatitis demonstrated clinical efficacy over 16 weeks of observation. These findings are consistent with the view of atopic dermatitis as an immune-inflammatory disease involving cytokine signaling pathways that sustain itching, skin inflammation, and epidermal barrier dysfunction. The main limitation of the study was the small sample size; therefore, multicenter studies with a larger number of patients are needed to clarify long-term efficacy and safety.