度普利尤单抗在儿童特应性皮炎中的长期有效性、安全性和生存情况

文献信息

中文摘要

重要性： 关于度普利尤单抗在临床环境中治疗儿童特应性皮炎（AD）患者的长期有效性和安全性的数据有限。
目的： 评估度普利尤单抗在各儿科年龄组中长达3年随访的临床有效性、安全性、药物生存情况以及停药的原因和相关因素。
设计、场所和参与者： 这项多中心、前瞻性队列研究（BioDay注册研究）于2019年11月至2025年10月在荷兰的4家学术医院和3家非学术医院开展，纳入开始接受度普利尤单抗治疗的中重度AD儿科患者（≤16岁）。数据分析时间为2025年9月至2026年1月。
暴露： 度普利尤单抗按说明书推荐剂量给药。如有临床指征则启动减量。
主要结局和指标： 临床有效性通过湿疹面积和严重程度指数（EASI）和研究者总体评估（IGA）进行评估。其他结局包括瘙痒数字评定量表（NRS）、疼痛NRS和生活质量（QoL）评分。安全性通过不良事件（AE）进行评估。评估了药物生存情况、停药原因及相关因素。
结果： 总体而言，309例AD儿科患者（平均[SD]年龄，10.2[4.2]岁；女性150例[48.5%]，男性159例[51.5%]）接受了度普利尤单抗治疗；基线时51例（16.5%）年龄为6个月至5岁（中位随访时间，45.0[IQR，26.0-101.0]周），120例（38.8%）年龄为6至11岁（中位随访时间，80.0[IQR，32.0-135.0]周），138例（44.7%）年龄为12至16岁（中位随访时间，89.5[IQR，48.0-143.0]周）。大多数患者AD维持控制，3年后EASI和瘙痒NRS平均评分仍较低（分别为3.4[95%CI，2.4-4.5]和3.6[95%CI，3.1-4.1]）。各年龄组在瘙痒NRS和QoL评分随时间变化方面存在显著差异，6个月至5岁儿童报告的评分始终高于年龄较大的儿童。最常报告的不良事件是度普利尤单抗相关眼表疾病（113例[36.6%]）。50例患者（50例[16.2%]）停用度普利尤单抗，主要原因是无效（19例[38.0%]）和/或不良事件（15例[30.0%]），或给药问题（11例[22.0%]）；大多数停药发生在1.5年内。3年药物生存率为80.1%；过敏性哮喘、过敏性鼻炎以及年龄6至11岁与较低的停药风险相关。
结论和意义： 这项队列研究的结果提示，度普利尤单抗在临床环境中对儿童AD具有长期有效性和安全性。年龄较小的儿童瘙痒NRS评分更高、QoL损害更大，并且因给药问题而更常停药，凸显了年龄特异性的挑战。

英文摘要

IMPORTANCE: Limited data are available on the long-term effectiveness and safety of dupilumab in pediatric patients with atopic dermatitis (AD) in a clinical setting.
OBJECTIVE: To assess the clinical effectiveness, safety, drug survival, and reasons and associated factors for discontinuation of dupilumab across pediatric age groups with up to 3 years of follow-up.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, prospective cohort study (BioDay Registry) was conducted across 4 academic and 3 nonacademic hospitals in the Netherlands from November 2019 to October 2025 and included pediatric patients (≤16 years) with moderate to severe AD who initiated treatment with dupilumab. Data were analyzed from September 2025 to January 2026.
EXPOSURE(S): Dupilumab was administered at the label-recommended dose. Dose reduction was initiated if clinically indicated.
MAIN OUTCOMES AND MEASURES: Clinical effectiveness was evaluated by the Eczema Area and Severity Index (EASI) and Investigator Global Assessment (IGA). Additional outcomes included the Numeric Rating Scale (NRS) for pruritus, NRS for pain, and quality of life (QoL) scores. Safety was assessed by adverse events (AEs). Drug survival, reasons, and factors associated with discontinuation were evaluated.
RESULTS: Overall, 309 pediatric patients with AD (mean [SD] age, 10.2 [4.2] years; 150 female individuals [48.5%] and 159 male individuals [51.5%]) were treated with dupilumab; 51 (16.5%) were aged 6 months to 5 years (median follow-up, 45.0 [IQR, 26.0-101.0] weeks), 120 (38.8%) were aged 6 to 11 years (median follow-up, 80.0 [IQR, 32.0-135.0] weeks), and 138 (44.7%) were aged 12 to 16 years (median follow-up, 89.5 [IQR, 48.0-143.0] weeks) at baseline. Most patients maintained controlled AD, with mean EASI and NRS scores for pruritus remaining low after 3 years (3.4 [95% CI, 2.4-4.5] and 3.6 [95% CI, 3.1-4.1], respectively). Age groups differed significantly in NRS for pruritus and QoL scores over time, with children aged 6 months to 5 years consistently reporting higher scores than older children. The most frequently reported AE was dupilumab-associated ocular surface disease (113 [36.6%]). Fifty patients (50 [16.2%]) discontinued dupilumab, mainly due to ineffectiveness (19 [38.0%]) and/or AEs (15 [30.0%]), or administration problems (11 [22.0%]); most discontinuations occurred within 1.5 years. Three-year drug survival was 80.1%; allergic asthma, allergic rhinitis, and being age 6 to 11 years were associated with a lower risk of discontinuation.
CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that dupilumab demonstrates long-term effectiveness and safety in pediatric AD in a clinical setting. Younger children show higher NRS scores for pruritus and greater QoL impairment and discontinue treatment more often due to administration problems, highlighting age-specific challenges.