度普利尤单抗在6个月至6岁以下中重度特应性皮炎患儿中的疗效及早期超级应答者的临床特征

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中文摘要

背景： 评估度普利尤单抗治疗6个月至6岁儿童中重度特应性皮炎（AD）的疗效，并探讨影响早期超级应答者（eSR）的临床特征。
方法： 本研究采用前瞻性设计，纳入2023年1月至2025年3月在宁夏医科大学总医院皮肤科接受治疗的中重度AD患儿。根据患儿年龄和体重，每4周皮下注射度普利尤单抗（200-300 mg）。在基线、治疗第4周、第12周和第16周，使用以下工具评估度普利尤单抗的疗效及家庭生活质量：湿疹面积和严重程度指数（EASI）、研究者总体评估（IGA）、峰值瘙痒数字评定量表（PP-NRS）、儿童皮肤病生活质量指数（CDLQI）/婴儿皮肤病生活质量指数（IDQoL）以及皮炎家庭影响（DFI）。使用鼻结膜炎控制评估测试（RCAT）、儿童哮喘控制测试（C-ACT）和口服食物激发试验（OFC）评估共病情况的改善。此外，系统记录治疗期间发生的不良事件。记录第4周同时达到EASI75（EASI评分较基线改善≥75%）、PP-NRS降低≥4分且CDLQI/IDQoL改善≥4分的患者比例，以及第16周同时达到EASI75和IGA 0/1（清除/几乎清除）的患者比例。采用线性混合模型分析度普利尤单抗治疗前后不同时间点临床评分的变化，并应用logistic回归识别影响度普利尤单抗治疗eSR的因素。
结果： 本研究共纳入50例中重度AD患儿，其中男性21例（42.00%），女性29例（58.00%），年龄4.24±1.81岁。度普利尤单抗治疗后第4、12和16周，与皮肤病变和瘙痒相关的临床评分均显著低于基线（P< 0.001）。第4周时，40.00%（20/50）的患者达到主要疗效终点。至第16周，分别有87.10%（27/31）和90.32%（28/31）的患者达到EASI75和IGA 0/1。DFI评分为重度/中度的患者比例从基线的100%显著降至9.68%（P < 0.001）。值得注意的是，反复上呼吸道感染的患病率显著下降（P = 0.017），而过敏性鼻炎和食物过敏的改善率分别达到84.21%（P < 0.001）和84.61%（P < 0.001）。多因素logistic回归显示，高绝对嗜碱性粒细胞计数（OR = 0.104，95% CI = 0.021-0.506，P = 0.005）和存在过敏性鼻炎（OR = 0.223，95% CI = 0.055-0.896，P = 0.035）是eSR的独立预测因素。受试者工作特征（ROC）曲线分析显示出较高的预测准确性（AUC = 0.773；P = 0.001），表明基线绝对嗜碱性粒细胞计数低于0.035×109/L与度普利尤单抗更好的eSR相关。治疗期间未观察到严重不良事件。
结论： 度普利尤单抗在治疗6个月至6岁儿童中重度特应性皮炎方面显示出显著疗效和良好的安全性。治疗期间，患者过敏性共病减轻，反复上呼吸道感染发生率下降，患儿及其家庭的生活质量改善。外周血绝对嗜碱性粒细胞计数升高和存在过敏性鼻炎是AD患儿对度普利尤单抗eSR的独立预测因素。

英文摘要

BACKGROUND: To evaluate the efficacy of dupilumab in treating moderate-to-severe atopic dermatitis (AD) in children aged 6 months to 6 years and to investigate the clinical characteristics influencing early super-responders（eSR).
METHODS: This study adopted a prospective design and enrolled pediatric patients with moderate-to-severe AD who were treated at the Department of Dermatology, General Hospital of Ningxia Medical University, from January 2023 to March 2025. In accordance with the patients' age and body weight, a subcutaneous injection of dupilumab (200-300 mg) was administered every 4 weeks. At baseline, week 4, week 12, and week 16 of treatment, the efficacy of dupilumab and the family quality of life were evaluated using the following tools: the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Peak Pruritus Numeric Rating Scale (PP-NRS), Children's Dermatology Life Quality Index (CDLQI)/Infant's Dermatology Life Quality Index (IDQoL), and Dermatitis Family Impact (DFI). Improvements in comorbid conditions were assessed using the Rhinoconjunctivitis Control Assessment Test (RCAT), Child Asthma Control Test (C-ACT), and Oral Food Challenge (OFC). Moreover, adverse events that occurred during the treatment period were recorded systematically. The proportions of patients who achieved EASI75 (≥75% improvement in EASI score from baseline), a ≥4-point reduction in PP-NRS, and a ≥4-point improvement in CDLQI / IDQoL concurrently at week 4, as well as those who met both EASI75 and IGA 0/1(clear/almost clear) at week 16, were documented. Linear mixed models were used to analyze changes in clinical scores at different time points before and after dupilumab treatment, and logistic regression was applied to identify factors influencing eSR to dupilumab treatment.
RESULTS: A total of 50 children with moderate to severe AD, including 21 males (42.00%) and 29 females (58.00%), aged 4.24±1.81, were included in this study. Clinical scores related to skin lesions and pruritus were significantly lower at weeks 4, 12, and 16 postdupilumab treatment than at baseline (P< 0.001). At week 4, 40.00% (20/50) of patients achieved the primary efficacy endpoints. By week 16, 87.10% (27/31) and 90.32% (28/31) of patients had EASI75 and an IGA 0/1, respectively. The proportion of patients with severe/moderate DFI scores decreased markedly from 100% at baseline to 9.68% (P < 0.001). Notably, the prevalence of recurrent upper respiratory tract infections decreased significantly (P = 0.017), while the improvement rates for allergic rhinitis and food allergies reached 84.21% (P < 0.001) and 84.61% (P < 0.001), respectively. Multivariate logistic regression revealed that a high absolute basophil count (OR = 0.104, 95% CI = 0.021-0.506, P = 0.005) and the presence of allergic rhinitis (OR = 0.223, 95% CI = 0.055-0.896, P = 0.035) were independent predictors of eSR. Receiver operating characteristic (ROC) curve analysis demonstrated high predictive accuracy (AUC = 0.773; P = 0.001), indicating that a baseline absolute basophil count less than 0.035×109/L was associated with a better eSR to dupilumab. No serious adverse events were observed during treatment.
CONCLUSION: Dupilumab demonstrates significant efficacy and a favorable safety profile in the treatment of moderate-to-severe atopic dermatitis in children aged 6 months to 6 years. During treatment, patients presented alleviated allergic comorbidities, decreased incidence of recurrent upper respiratory tract infections, and improved quality of life for children and their families. Elevated absolute basophil count in peripheral blood and the presence of allergic rhinitis were independent predictors of eSR to dupilumab in children with AD.