Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data

Amy S. Paller; Lisa A. Beck; Andrew Blauvelt; Elaine C. Siegfried; Michael J. Cork; Andreas Wollenberg; Zhen Chen; Faisal A. Khokhar; Jignesh Vakil; Annie Zhang; Ashish Bansal; Sonya L. Cyr

doi:10.1111/pde.14909

Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data

Amy S. Paller, Lisa A. Beck, Andrew Blauvelt, Elaine C. Siegfried, Michael J. Cork, Andreas Wollenberg, Zhen Chen, Faisal A. Khokhar, Jignesh Vakil, Annie Zhang, Ashish Bansal, Sonya L. Cyr^*

^*Corresponding author for this work

Dermatology

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

26 Scopus citations

Abstract

Background/Objective: Patients with moderate-to-severe atopic dermatitis (AD) have increased risk of cutaneous and extracutaneous infections. Dupilumab has previously been associated with reduced risk of serious/severe infections and non-herpetic skin infections in adults with moderate-to-severe AD. This analysis assessed infection rates with dupilumab versus placebo in pediatric patients with moderate-to-severe and severe AD participating in clinical trials. Methods: This is a pooled analysis from two 16-week, randomized, placebo-controlled, phase 3 clinical trials of dupilumab: monotherapy in adolescents aged 12–17 years with moderate-to-severe AD (LIBERTY AD ADOL, NCT03054428) and with concomitant topical corticosteroids in children aged 6–11 years with severe AD (LIBERTY AD PEDS, NCT03345914). Data were pooled according to treatment received: placebo/approved dupilumab doses/other studied dupilumab doses/all dupilumab doses. Exposure-adjusted rates (patients with ≥1 event per 100 patient-years [nP/100 PY]) were used to compare treatment groups. Results: Overall, 612 patients were included: 205 received placebo and 407 received dupilumab (261 received approved dupilumab doses and 146 received other studied dupilumab doses). Overall infection rates were numerically lower with dupilumab versus placebo (nP/100 PY: placebo, 227; approved dupilumab, 173; other dupilumab, 206; all dupilumab, 184). Total skin infections were numerically less frequent in all dupilumab-treated groups versus placebo (nP/100 PY: placebo, 67; approved dupilumab, 30; other dupilumab, 46; all dupilumab, 36). Conclusions: These data suggest that dupilumab treatment in children and adolescents with AD does not increase infection risk overall and is associated with lower rates of skin infections compared with placebo.

Original language	English (US)
Pages (from-to)	187-196
Number of pages	10
Journal	Pediatric dermatology
Volume	39
Issue number	2
DOIs	https://doi.org/10.1111/pde.14909
State	Published - Mar 1 2022

Funding

The authors would like to thank Brad Shumel, MD, of Regeneron Pharmaceuticals, Inc., for his considerable contributions to the development of this manuscript. Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT03054428, NCT03345914. Medical writing/editorial assistance provided by Lola MacRae, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. according to the . Good Publication Practice guideline Paller has served as an investigator for AbbVie, AnaptysBio, Eli Lilly, Incyte, Janssen, Lenus Pharma, LEO Pharma, Novartis, Regeneron Pharmaceuticals, Inc., and UCB; and a consultant for AbbVie, Abeona Therapeutics, Almirall, Asana Biosciences, Boehringer Ingelheim, BridgeBio Pharma, Dermavant, Dermira, Eli Lilly, Exicure, Forté, Galderma, Incyte, InMed Pharmaceuticals, Janssen, LEO Pharma, LifeMax, Novartis, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Sol‐Gel, and UCB. Beck has received honoraria as a consultant from AbbVie, Allakos, Arena Pharma, AstraZeneca, Connect Biopharma, Eli Lilly, LEO Pharma, Novan, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB, and Vimalan; has received grants for clinical trials from AbbVie, LEO Pharma, Pfizer, and Regeneron Pharmaceuticals, Inc.; and holds stock in Pfizer and Medtronic. Blauvelt has served as a scientific advisor and/or clinical study investigator for AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, LEO Pharma, Novartis, Pfizer, Rapt, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Sun Pharma, and UCB. Siegfried has served as a scientific advisor and/or clinical study investigator for Eli Lilly, Janssen, Novartis, Novan, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, UCB, and Verrica; as a paid speaker for Regeneron Pharmaceuticals, Inc.; and as a DSMB member for GSK, LEO Pharma, Novan, Pfizer, and UCB. Cork has served as a consultant and/or advisory board member and/or received research grants from Almirall, Amgen, Astellas, Bayer, GSK, Hyphens Pharma, Johnson & Johnson, LEO Pharma, Novartis, Perrigo L’Oreal, Pfizer, Sanofi, Stiefel, Regeneron Pharmaceuticals, Inc., and Unilever. Wollenberg has served as an investigator for Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, and UCB; as a consultant for AbbVie, Almirall, Anacor, Arena, Eli Lilly, Galapagos, Galderma, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., and Sanofi Genzyme; and has received research grants from LEO Pharma and Pierre Fabre. Chen, Khokhar, Bansal, and Cyr are employees and shareholders of Regeneron Pharmaceuticals, Inc. Vakil and Zhang are employees and may hold stock and/or stock options in Sanofi Genzyme.

Keywords

IL-13
IL-4
atopic dermatitis
dupilumab
herpetic skin infections
skin infections
systemic infections

ASJC Scopus subject areas

Dermatology
Pediatrics, Perinatology, and Child Health

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10.1111/pde.14909

Cite this

Paller, A. S., Beck, L. A., Blauvelt, A., Siegfried, E. C., Cork, M. J., Wollenberg, A., Chen, Z., Khokhar, F. A., Vakil, J., Zhang, A., Bansal, A., & Cyr, S. L. (2022). Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data. Pediatric dermatology, 39(2), 187-196. https://doi.org/10.1111/pde.14909

@article{dcd7d8ff7e564d7aae2c771f621bed7a,

title = "Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data",

abstract = "Background/Objective: Patients with moderate-to-severe atopic dermatitis (AD) have increased risk of cutaneous and extracutaneous infections. Dupilumab has previously been associated with reduced risk of serious/severe infections and non-herpetic skin infections in adults with moderate-to-severe AD. This analysis assessed infection rates with dupilumab versus placebo in pediatric patients with moderate-to-severe and severe AD participating in clinical trials. Methods: This is a pooled analysis from two 16-week, randomized, placebo-controlled, phase 3 clinical trials of dupilumab: monotherapy in adolescents aged 12–17 years with moderate-to-severe AD (LIBERTY AD ADOL, NCT03054428) and with concomitant topical corticosteroids in children aged 6–11 years with severe AD (LIBERTY AD PEDS, NCT03345914). Data were pooled according to treatment received: placebo/approved dupilumab doses/other studied dupilumab doses/all dupilumab doses. Exposure-adjusted rates (patients with ≥1 event per 100 patient-years [nP/100 PY]) were used to compare treatment groups. Results: Overall, 612 patients were included: 205 received placebo and 407 received dupilumab (261 received approved dupilumab doses and 146 received other studied dupilumab doses). Overall infection rates were numerically lower with dupilumab versus placebo (nP/100 PY: placebo, 227; approved dupilumab, 173; other dupilumab, 206; all dupilumab, 184). Total skin infections were numerically less frequent in all dupilumab-treated groups versus placebo (nP/100 PY: placebo, 67; approved dupilumab, 30; other dupilumab, 46; all dupilumab, 36). Conclusions: These data suggest that dupilumab treatment in children and adolescents with AD does not increase infection risk overall and is associated with lower rates of skin infections compared with placebo.",

keywords = "IL-13, IL-4, atopic dermatitis, dupilumab, herpetic skin infections, skin infections, systemic infections",

author = "Paller, {Amy S.} and Beck, {Lisa A.} and Andrew Blauvelt and Siegfried, {Elaine C.} and Cork, {Michael J.} and Andreas Wollenberg and Zhen Chen and Khokhar, {Faisal A.} and Jignesh Vakil and Annie Zhang and Ashish Bansal and Cyr, {Sonya L.}",

note = "Publisher Copyright: {\textcopyright} 2022 Regeneron Pharmaceuticals, Inc. Pediatric Dermatology published by Wiley Periodicals LLC.",

year = "2022",

month = mar,

day = "1",

doi = "10.1111/pde.14909",

language = "English (US)",

volume = "39",

pages = "187--196",

journal = "Pediatric dermatology",

issn = "0736-8046",

publisher = "Wiley-Blackwell",

number = "2",

}

Paller, AS, Beck, LA, Blauvelt, A, Siegfried, EC, Cork, MJ, Wollenberg, A, Chen, Z, Khokhar, FA, Vakil, J, Zhang, A, Bansal, A & Cyr, SL 2022, 'Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data', Pediatric dermatology, vol. 39, no. 2, pp. 187-196. https://doi.org/10.1111/pde.14909

TY - JOUR

T1 - Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data

AU - Paller, Amy S.

AU - Beck, Lisa A.

AU - Blauvelt, Andrew

AU - Siegfried, Elaine C.

AU - Cork, Michael J.

AU - Wollenberg, Andreas

AU - Chen, Zhen

AU - Khokhar, Faisal A.

AU - Vakil, Jignesh

AU - Zhang, Annie

AU - Bansal, Ashish

AU - Cyr, Sonya L.

PY - 2022/3/1

Y1 - 2022/3/1

N2 - Background/Objective: Patients with moderate-to-severe atopic dermatitis (AD) have increased risk of cutaneous and extracutaneous infections. Dupilumab has previously been associated with reduced risk of serious/severe infections and non-herpetic skin infections in adults with moderate-to-severe AD. This analysis assessed infection rates with dupilumab versus placebo in pediatric patients with moderate-to-severe and severe AD participating in clinical trials. Methods: This is a pooled analysis from two 16-week, randomized, placebo-controlled, phase 3 clinical trials of dupilumab: monotherapy in adolescents aged 12–17 years with moderate-to-severe AD (LIBERTY AD ADOL, NCT03054428) and with concomitant topical corticosteroids in children aged 6–11 years with severe AD (LIBERTY AD PEDS, NCT03345914). Data were pooled according to treatment received: placebo/approved dupilumab doses/other studied dupilumab doses/all dupilumab doses. Exposure-adjusted rates (patients with ≥1 event per 100 patient-years [nP/100 PY]) were used to compare treatment groups. Results: Overall, 612 patients were included: 205 received placebo and 407 received dupilumab (261 received approved dupilumab doses and 146 received other studied dupilumab doses). Overall infection rates were numerically lower with dupilumab versus placebo (nP/100 PY: placebo, 227; approved dupilumab, 173; other dupilumab, 206; all dupilumab, 184). Total skin infections were numerically less frequent in all dupilumab-treated groups versus placebo (nP/100 PY: placebo, 67; approved dupilumab, 30; other dupilumab, 46; all dupilumab, 36). Conclusions: These data suggest that dupilumab treatment in children and adolescents with AD does not increase infection risk overall and is associated with lower rates of skin infections compared with placebo.

AB - Background/Objective: Patients with moderate-to-severe atopic dermatitis (AD) have increased risk of cutaneous and extracutaneous infections. Dupilumab has previously been associated with reduced risk of serious/severe infections and non-herpetic skin infections in adults with moderate-to-severe AD. This analysis assessed infection rates with dupilumab versus placebo in pediatric patients with moderate-to-severe and severe AD participating in clinical trials. Methods: This is a pooled analysis from two 16-week, randomized, placebo-controlled, phase 3 clinical trials of dupilumab: monotherapy in adolescents aged 12–17 years with moderate-to-severe AD (LIBERTY AD ADOL, NCT03054428) and with concomitant topical corticosteroids in children aged 6–11 years with severe AD (LIBERTY AD PEDS, NCT03345914). Data were pooled according to treatment received: placebo/approved dupilumab doses/other studied dupilumab doses/all dupilumab doses. Exposure-adjusted rates (patients with ≥1 event per 100 patient-years [nP/100 PY]) were used to compare treatment groups. Results: Overall, 612 patients were included: 205 received placebo and 407 received dupilumab (261 received approved dupilumab doses and 146 received other studied dupilumab doses). Overall infection rates were numerically lower with dupilumab versus placebo (nP/100 PY: placebo, 227; approved dupilumab, 173; other dupilumab, 206; all dupilumab, 184). Total skin infections were numerically less frequent in all dupilumab-treated groups versus placebo (nP/100 PY: placebo, 67; approved dupilumab, 30; other dupilumab, 46; all dupilumab, 36). Conclusions: These data suggest that dupilumab treatment in children and adolescents with AD does not increase infection risk overall and is associated with lower rates of skin infections compared with placebo.

KW - IL-13

KW - IL-4

KW - atopic dermatitis

KW - dupilumab

KW - herpetic skin infections

KW - skin infections

KW - systemic infections

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Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data

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