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

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

doi:10.1007/s40272-023-00611-9

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

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^*

^*Corresponding author for this work

Dermatology

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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: (Figure presented.).

Original language	English (US)
Pages (from-to)	163-173
Number of pages	11
Journal	Pediatric Drugs
Volume	26
Issue number	2
DOIs	https://doi.org/10.1007/s40272-023-00611-9
State	Published - Mar 2024

Funding

This research was sponsored by Sanofi and Regeneron Pharmaceuticals Inc.; ClinicalTrials.gov Identifier: NCT03346434. Medical writing/editorial assistance was provided by Alessandra Iannino, PhD, of Excerpta Medica, and was funded by Sanofi and Regeneron Pharmaceuticals Inc., according to the Good Publication Practice Guidelines. The authors would like to thank the patients and their caregivers for their participation, and publication managers Adriana Mello of Sanofi and Linda Williams of Regeneron Pharmaceuticals Inc., who provided support and input. The National Institute for Health and Care Research provided support to the Manchester Clinical Research Facility at the Royal Manchester Children’s Hospital. This research was sponsored by Sanofi and Regeneron Pharmaceuticals Inc.; ClinicalTrials.gov Identifier: NCT03346434. Medical writing/editorial assistance was provided by Alessandra Iannino, PhD, of Excerpta Medica, and was funded by Sanofi and Regeneron Pharmaceuticals Inc., according to the Good Publication Practice Guidelines. The authors would like to thank the patients and their caregivers for their participation, and publication managers Adriana Mello of Sanofi and Linda Williams of Regeneron Pharmaceuticals Inc., who provided support and input. The National Institute for Health and Care Research provided support to the Manchester Clinical Research Facility at the Royal Manchester Children’s Hospital.

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Pharmacology (medical)

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10.1007/s40272-023-00611-9

Cite this

Paller, A. S., Siegfried, E. C., Cork, M. J., Arkwright, P. D., Eichenfield, L. F., Ramien, M., Khokhar, F. A., Chen, Z., Zhang, A., & Cyr, S. L. (2024). Infections in Children Aged 6 Months to 5 Years Treated with Dupilumab in a Placebo-Controlled Clinical Trial of Moderate-to-Severe Atopic Dermatitis. Pediatric Drugs, 26(2), 163-173. https://doi.org/10.1007/s40272-023-00611-9

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

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: (Figure presented.).",

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doi = "10.1007/s40272-023-00611-9",

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T1 - Infections in Children Aged 6 Months to 5 Years Treated with Dupilumab in a Placebo-Controlled Clinical Trial of Moderate-to-Severe Atopic Dermatitis

AU - Paller, Amy S.

AU - Siegfried, Elaine C.

AU - Cork, Michael J.

AU - Arkwright, Peter D.

AU - Eichenfield, Lawrence F.

AU - Ramien, Michele

AU - Khokhar, Faisal A.

AU - Chen, Zhen

AU - Zhang, Annie

AU - Cyr, Sonya L.

PY - 2024/3

Y1 - 2024/3

N2 - 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: (Figure presented.).

AB - 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: (Figure presented.).

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

Abstract

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