Infections in Children Aged 6 Months to 5 Years Treated with Dupilumab in a Placebo-Controlled Clinical Trial of Moderate-to-Severe Atopic Dermatitis.

IF 3.4 3区医学 Q1 PEDIATRICS Pediatric Drugs Pub Date : 2024-03-01 Epub Date: 2024-01-24 DOI:10.1007/s40272-023-00611-9

Amy S Paller, Elaine C Siegfried, Michael J Cork, Peter D Arkwright, Lawrence F Eichenfield, Michele Ramien, Faisal A Khokhar, Zhen Chen, Annie Zhang, Sonya L Cyr

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Abstract

Background: Patients with atopic dermatitis (AD), particularly infants and young children, are at greater risk of developing skin infections. In this study, we assessed infection rates in AD patients aged 6 months to 5 years treated with dupilumab.

Methods: In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled, phase III clinical trial, children aged 6 months to 5 years with moderate-to-severe AD were randomized 1:1 to subcutaneous dupilumab or placebo, with concomitant low-potency topical corticosteroids, every 4 weeks for 16 weeks. Exposure-adjusted infection rates were used to compare treatment groups.

Results: The analysis included 162 patients, of whom 83 received dupilumab and 79 received placebo. Total infection rates were not significantly different between the dupilumab and placebo groups (rate ratio [RR] 0.75, 95% CI 0.48-1.19; p = 0.223). Non-herpetic adjudicated skin infections and bacterial infections were significantly less frequent with dupilumab versus placebo (non-herpetic skin infections: RR 0.46, 95% CI 0.21-0.99; p = 0.047; bacterial infections: RR 0.09, 95% CI 0.01-0.67; p = 0.019), and the number of patients using systemic anti-infective medication was significantly lower in the dupilumab group (RR 0.52, 95% CI 0.30-0.89; p = 0.019). There were no significant differences in the number of herpetic infections between the dupilumab and placebo groups (RR 1.17, 95% CI 0.31-4.35; p = 0.817). The number of patients with two or more infection events was significantly higher in the placebo group (RR 0.29, 95% CI 0.12-0.68; p = 0.004), and no severe or serious infections (including eczema herpeticum) were observed among patients receiving dupilumab.

Conclusions: These data suggest that dupilumab treatment in infants and children younger than 6 years with AD does not increase overall risk of infections and is associated with a reduced risk of bacterial and non-herpetic skin infections compared with placebo, resulting in a reduced need for anti-infective medication.

Trial registration: The trial was registered with ClinicalTrials.gov with ID number NCT03346434 on November 17, 2017. INFOGRAPHIC.

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中度至重度特应性皮炎安慰剂对照临床试验中使用杜匹单抗治疗的 6 个月至 5 岁儿童的感染情况。

背景：特应性皮炎（AD）患者，尤其是婴幼儿，患皮肤感染的风险更大。在这项研究中，我们评估了接受杜匹单抗治疗的 6 个月至 5 岁 AD 患者的感染率：在LIBERTY AD PRESCHOOL（一项双盲、安慰剂对照的III期临床试验）中，6个月至5岁的中重度AD患儿按1:1的比例随机接受皮下注射dupilumab或安慰剂治疗，同时使用低效局部皮质类固醇激素，每4周一次，共治疗16周。采用暴露调整感染率来比较治疗组：分析包括162名患者，其中83人接受了dupilumab治疗，79人接受了安慰剂治疗。dupilumab组和安慰剂组的总感染率无明显差异（比率比 [RR] 0.75，95% CI 0.48-1.19；P = 0.223）。与安慰剂相比，杜匹单抗治疗非疱疹性皮肤感染和细菌感染的频率明显降低（非疱疹性皮肤感染：RR 0.46，95% CI 0.48-1.19；P = 0.223）：RR为0.46，95% CI为0.21-0.99；P = 0.047；细菌感染：RR为0.09，95% CI为0.01-0.67；p = 0.019），使用全身抗感染药物的患者人数在杜鲁单抗组显著减少（RR为0.52，95% CI为0.30-0.89；p = 0.019）。杜杜单抗组和安慰剂组的疱疹感染数量没有明显差异（RR 1.17，95% CI 0.31-4.35；P = 0.817）。安慰剂组发生两次或两次以上感染的患者人数明显较多（RR 0.29，95% CI 0.12-0.68；p = 0.004），接受杜比鲁单抗治疗的患者中未观察到严重感染（包括疱疹性湿疹）：这些数据表明，与安慰剂相比，对6岁以下婴幼儿AD患者进行dupilumab治疗不会增加感染的总体风险，并能降低细菌性和非疱疹性皮肤感染的风险，从而减少对抗感染药物的需求：该试验于2017年11月17日在ClinicalTrials.gov注册，ID号为NCT03346434。INFOGRAPHIC.

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来源期刊

Pediatric Drugs PEDIATRICS-PHARMACOLOGY & PHARMACY

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Pediatric Drugs promotes the optimization and advancement of all aspects of pharmacotherapy for healthcare professionals interested in pediatric drug therapy (including vaccines). The program of review and original research articles provides healthcare decision makers with clinically applicable knowledge on issues relevant to drug therapy in all areas of neonatology and the care of children and adolescents. The Journal includes: -overviews of contentious or emerging issues. -comprehensive narrative reviews of topics relating to the effective and safe management of drug therapy through all stages of pediatric development. -practical reviews covering optimum drug management of specific clinical situations. -systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. -Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in the pediatric population. -original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Pediatric Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.