关键词: 皮炎, 特应性, 生物制剂, 度普利尤单抗, 治疗效果, 药物不良反应

Abstract: 【Abstract】 Objective To evaluate the efficacy of dupilumab in the treatment of moderate to severe atopic dermatitis （AD） in children, and to analyze its influencing factors. Methods A retrospective analysis was carried out on the demographic and clinical data collected from children with moderate to severe AD, who were treated with dupilumab in the Department of Dermatology, Xiangya Hospital, Central South University from October 2020 to October 2022. The initial dose （200 - 600 mg） of dupilumab was administered based on children′s age and weight, followed by 200 - 300 mg every 2 - 3 weeks. The curative efficacy and quality of life were evaluated using the Investigator's Global Assessment （IGA）, Eczema Area and Severity Index （EASI）, SCORing Atopic Dermatitis （SCORAD）, Peak Pruritus Numerical Rating Scale （PP-NRS）, Patient-Oriented Eczema Measure （POEM）, and the Children's Dermatology Life Quality Index （CDLQI）/Infants' Dermatitis Quality of Life Index （IDQoL） before treatment, and at weeks 4, 12, and 16 after treatment. Adverse events during the treatment period were also recorded. The main outcome indicators were the proportion of patients achieving IGA0/1 and EASI75 （≥ 75% improvement from baseline in EASI score） at week 16. Changes in the clinical scores and laboratory parameters at different time points after the treatment with dupilumab were analyzed using generalized estimating equations, and a logistic regression model was used to identify the influencing factors for EASI75 response at week 16. Results A total of 136 children aged 2 - 11 years met the diagnosis of moderate to severe AD and received at least one dose of dupilumab, among whom 123 children met the inclusion criteria for this analysis. IGA, EASI, SCORAD, POEM, CDLQI/IDQoL, and PP-NRS scores were significantly improved at weeks 4, 12, and 16 after dupilumab therapy compared with baseline scores （all P < 0.01）. At week 16, the proportions of patients achieving IGA0/1, EASI50, EASI75, EASI90, CDLQI/IDQoL improvement ≥ 4 points, and PP-NRS improvement ≥ 4 points were 44.6% （33/74）, 86.5% （64/74）, 70.3% （52/74）, 48.7% （36/74）, 56.8% （42/74）, and 77.0% （57/74）, respectively; the eosinophil counts significantly decreased compared with the baseline level （P = 0.001）. The total IgE levels at different time points after treatment did not differ from the baseline level （P > 0.01）. At week 16, the related factors for the response to dupilumab were relatively low ages （compared with the children aged 6 - 11 years, those aged 2 - 5 years showed lower EASI75 response rates: OR = 0.148, 95% CI: 0.027 - 0.823, P = 0.029） and having a family history of urticaria （OR = 0.033, 95% CI: 0.002 - 0.601, P = 0.021）, while gender, AD duration, subtypes and main clinical phenotypes of AD, allergic history, family history of atopic diseases, presence of serum allergen-specific IgE antibodies, serum total IgE levels, or eosinophil counts did not affect the efficacy of dupilumab （all P > 0.05）. During the 16-week treatment, 3 children discontinued the dupilumab treatment due to disease exacerbation, and 1 child developed conjunctivitis. Conclusions Dupilumab could effectively improve the symptoms and signs of children with moderate to severe AD whose condition was poorly controlled by conventional treatments, with a low incidence rate of adverse reactions. Relatively low ages and having a family history of urticaria may be negative factors influencing the efficacy of dupilumab in children with moderate to severe AD at week 16.

Key words: Dermatitis, atopic, Biological agents, Dupilumab, Therapeutic effect, Adverse drug reactions