The Posology of Dupilumab in Pediatric Patients With Atopic Dermatitis

Mohamed A. Kamal; Pavel Kovalenko; Matthew P. Kosloski; Kamal Srinivasan; Yi Zhang; Manoj Rajadhyaksha; Ching Ha Lai; Vanaja Kanamaluru; Christine Xu; Xian Sun; Eric L. Simpson; Amy S. Paller; Elaine C. Siegfried; Brad Shumel; Ashish Bansal; Nidal Al-Huniti; John D. Davis

doi:10.1002/cpt.2366

The Posology of Dupilumab in Pediatric Patients With Atopic Dermatitis

Mohamed A. Kamal^*, Pavel Kovalenko, Matthew P. Kosloski, Kamal Srinivasan, Yi Zhang, Manoj Rajadhyaksha, Ching Ha Lai, Vanaja Kanamaluru, Christine Xu, Xian Sun, Eric L. Simpson, Amy S. Paller, Elaine C. Siegfried, Brad Shumel, Ashish Bansal, Nidal Al-Huniti, John D. Davis

^*Corresponding author for this work

Dermatology

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

10 Scopus citations

Abstract

Dupilumab demonstrated efficacy with an acceptable safety profile in two randomized, double-blind, placebo-controlled, parallel-group, phase III trials in adolescents (12–17 years; LIBERTY AD ADOL) and children (6–11 years; LIBERTY AD PEDS) with atopic dermatitis (AD) treated for 16 weeks. Here, we present the pharmacokinetic profiles and exposure-response (E-R) relationships of dupilumab that guided the posology in these populations. A total of 251 adolescent patients with moderate-to-severe AD were randomized to subcutaneous dupilumab monotherapy every 2 weeks (q2w; 200 mg q2w, baseline weight < 60 kg; 300 mg q2w, ≥ 60 kg), dupilumab 300 mg every 4 weeks (q4w; non-weight tiered), or placebo; 367 children with severe AD were randomized to dupilumab q2w (100 mg q2w, baseline weight < 30 kg; 200 mg q2w, ≥ 30 kg), dupilumab 300 mg q4w, or placebo. Children received concomitant topical corticosteroids in addition to dupilumab, and loading doses were administered at the start of therapy. Mean dupilumab trough concentrations at week 16 for weight subcategories in each dosing regimen were compared with adult exposures for the approved dupilumab 300 mg q2w regimen. Positive E-R relationships were demonstrated between dupilumab trough concentrations and AD outcome measures across patient populations and regimens; no relationship was observed with treatment-emergent conjunctivitis. Based on these analyses, a weight-tiered posology was proposed for adolescents (200/300 mg q2w in patients 30–< 60 kg/≥ 60 kg) and children (300 mg q4w in patients 15–< 30 kg, 200 mg q2w in patients 30–< 60 kg) with moderate-to-severe AD.

Original language	English (US)
Pages (from-to)	1318-1328
Number of pages	11
Journal	Clinical pharmacology and therapeutics
Volume	110
Issue number	5
DOIs	https://doi.org/10.1002/cpt.2366
State	Published - Nov 2021

Funding

This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing and editorial support were provided by Jamie Lim, PhD, and Lola MacRae, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline. The authors acknowledge Dinesh Putluri and Hong Yan of Regeneron Pharmaceuticals, Inc. for their contributions. Medical writing and editorial support were provided by Jamie Lim, PhD, and Lola MacRae, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline. The authors acknowledge Dinesh Putluri and Hong Yan of Regeneron Pharmaceuticals, Inc. for their contributions.

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

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10.1002/cpt.2366

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Kamal, M. A., Kovalenko, P., Kosloski, M. P., Srinivasan, K., Zhang, Y., Rajadhyaksha, M., Lai, C. H., Kanamaluru, V., Xu, C., Sun, X., Simpson, E. L., Paller, A. S., Siegfried, E. C., Shumel, B., Bansal, A., Al-Huniti, N., & Davis, J. D. (2021). The Posology of Dupilumab in Pediatric Patients With Atopic Dermatitis. Clinical pharmacology and therapeutics, 110(5), 1318-1328. https://doi.org/10.1002/cpt.2366

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title = "The Posology of Dupilumab in Pediatric Patients With Atopic Dermatitis",

abstract = "Dupilumab demonstrated efficacy with an acceptable safety profile in two randomized, double-blind, placebo-controlled, parallel-group, phase III trials in adolescents (12–17 years; LIBERTY AD ADOL) and children (6–11 years; LIBERTY AD PEDS) with atopic dermatitis (AD) treated for 16 weeks. Here, we present the pharmacokinetic profiles and exposure-response (E-R) relationships of dupilumab that guided the posology in these populations. A total of 251 adolescent patients with moderate-to-severe AD were randomized to subcutaneous dupilumab monotherapy every 2 weeks (q2w; 200 mg q2w, baseline weight < 60 kg; 300 mg q2w, ≥ 60 kg), dupilumab 300 mg every 4 weeks (q4w; non-weight tiered), or placebo; 367 children with severe AD were randomized to dupilumab q2w (100 mg q2w, baseline weight < 30 kg; 200 mg q2w, ≥ 30 kg), dupilumab 300 mg q4w, or placebo. Children received concomitant topical corticosteroids in addition to dupilumab, and loading doses were administered at the start of therapy. Mean dupilumab trough concentrations at week 16 for weight subcategories in each dosing regimen were compared with adult exposures for the approved dupilumab 300 mg q2w regimen. Positive E-R relationships were demonstrated between dupilumab trough concentrations and AD outcome measures across patient populations and regimens; no relationship was observed with treatment-emergent conjunctivitis. Based on these analyses, a weight-tiered posology was proposed for adolescents (200/300 mg q2w in patients 30–< 60 kg/≥ 60 kg) and children (300 mg q4w in patients 15–< 30 kg, 200 mg q2w in patients 30–< 60 kg) with moderate-to-severe AD.",

author = "Kamal, {Mohamed A.} and Pavel Kovalenko and Kosloski, {Matthew P.} and Kamal Srinivasan and Yi Zhang and Manoj Rajadhyaksha and Lai, {Ching Ha} and Vanaja Kanamaluru and Christine Xu and Xian Sun and Simpson, {Eric L.} and Paller, {Amy S.} and Siegfried, {Elaine C.} and Brad Shumel and Ashish Bansal and Nidal Al-Huniti and Davis, {John D.}",

note = "Funding Information: This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing and editorial support were provided by Jamie Lim, PhD, and Lola MacRae, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline. The authors acknowledge Dinesh Putluri and Hong Yan of Regeneron Pharmaceuticals, Inc. for their contributions. Funding Information: Medical writing and editorial support were provided by Jamie Lim, PhD, and Lola MacRae, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline. The authors acknowledge Dinesh Putluri and Hong Yan of Regeneron Pharmaceuticals, Inc. for their contributions. Publisher Copyright: {\textcopyright} 2021 Regeneron Pharmaceuticals, Inc. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics",

year = "2021",

month = nov,

doi = "10.1002/cpt.2366",

language = "English (US)",

volume = "110",

pages = "1318--1328",

journal = "Clinical pharmacology and therapeutics",

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Kamal, MA, Kovalenko, P, Kosloski, MP, Srinivasan, K, Zhang, Y, Rajadhyaksha, M, Lai, CH, Kanamaluru, V, Xu, C, Sun, X, Simpson, EL, Paller, AS, Siegfried, EC, Shumel, B, Bansal, A, Al-Huniti, N & Davis, JD 2021, 'The Posology of Dupilumab in Pediatric Patients With Atopic Dermatitis', Clinical pharmacology and therapeutics, vol. 110, no. 5, pp. 1318-1328. https://doi.org/10.1002/cpt.2366

TY - JOUR

T1 - The Posology of Dupilumab in Pediatric Patients With Atopic Dermatitis

AU - Kamal, Mohamed A.

AU - Kovalenko, Pavel

AU - Kosloski, Matthew P.

AU - Srinivasan, Kamal

AU - Zhang, Yi

AU - Rajadhyaksha, Manoj

AU - Lai, Ching Ha

AU - Kanamaluru, Vanaja

AU - Xu, Christine

AU - Sun, Xian

AU - Simpson, Eric L.

AU - Paller, Amy S.

AU - Siegfried, Elaine C.

AU - Shumel, Brad

AU - Bansal, Ashish

AU - Al-Huniti, Nidal

AU - Davis, John D.

N1 - Funding Information: This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing and editorial support were provided by Jamie Lim, PhD, and Lola MacRae, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline. The authors acknowledge Dinesh Putluri and Hong Yan of Regeneron Pharmaceuticals, Inc. for their contributions. Funding Information: Medical writing and editorial support were provided by Jamie Lim, PhD, and Lola MacRae, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline. The authors acknowledge Dinesh Putluri and Hong Yan of Regeneron Pharmaceuticals, Inc. for their contributions. Publisher Copyright: © 2021 Regeneron Pharmaceuticals, Inc. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics

PY - 2021/11

Y1 - 2021/11

N2 - Dupilumab demonstrated efficacy with an acceptable safety profile in two randomized, double-blind, placebo-controlled, parallel-group, phase III trials in adolescents (12–17 years; LIBERTY AD ADOL) and children (6–11 years; LIBERTY AD PEDS) with atopic dermatitis (AD) treated for 16 weeks. Here, we present the pharmacokinetic profiles and exposure-response (E-R) relationships of dupilumab that guided the posology in these populations. A total of 251 adolescent patients with moderate-to-severe AD were randomized to subcutaneous dupilumab monotherapy every 2 weeks (q2w; 200 mg q2w, baseline weight < 60 kg; 300 mg q2w, ≥ 60 kg), dupilumab 300 mg every 4 weeks (q4w; non-weight tiered), or placebo; 367 children with severe AD were randomized to dupilumab q2w (100 mg q2w, baseline weight < 30 kg; 200 mg q2w, ≥ 30 kg), dupilumab 300 mg q4w, or placebo. Children received concomitant topical corticosteroids in addition to dupilumab, and loading doses were administered at the start of therapy. Mean dupilumab trough concentrations at week 16 for weight subcategories in each dosing regimen were compared with adult exposures for the approved dupilumab 300 mg q2w regimen. Positive E-R relationships were demonstrated between dupilumab trough concentrations and AD outcome measures across patient populations and regimens; no relationship was observed with treatment-emergent conjunctivitis. Based on these analyses, a weight-tiered posology was proposed for adolescents (200/300 mg q2w in patients 30–< 60 kg/≥ 60 kg) and children (300 mg q4w in patients 15–< 30 kg, 200 mg q2w in patients 30–< 60 kg) with moderate-to-severe AD.

AB - Dupilumab demonstrated efficacy with an acceptable safety profile in two randomized, double-blind, placebo-controlled, parallel-group, phase III trials in adolescents (12–17 years; LIBERTY AD ADOL) and children (6–11 years; LIBERTY AD PEDS) with atopic dermatitis (AD) treated for 16 weeks. Here, we present the pharmacokinetic profiles and exposure-response (E-R) relationships of dupilumab that guided the posology in these populations. A total of 251 adolescent patients with moderate-to-severe AD were randomized to subcutaneous dupilumab monotherapy every 2 weeks (q2w; 200 mg q2w, baseline weight < 60 kg; 300 mg q2w, ≥ 60 kg), dupilumab 300 mg every 4 weeks (q4w; non-weight tiered), or placebo; 367 children with severe AD were randomized to dupilumab q2w (100 mg q2w, baseline weight < 30 kg; 200 mg q2w, ≥ 30 kg), dupilumab 300 mg q4w, or placebo. Children received concomitant topical corticosteroids in addition to dupilumab, and loading doses were administered at the start of therapy. Mean dupilumab trough concentrations at week 16 for weight subcategories in each dosing regimen were compared with adult exposures for the approved dupilumab 300 mg q2w regimen. Positive E-R relationships were demonstrated between dupilumab trough concentrations and AD outcome measures across patient populations and regimens; no relationship was observed with treatment-emergent conjunctivitis. Based on these analyses, a weight-tiered posology was proposed for adolescents (200/300 mg q2w in patients 30–< 60 kg/≥ 60 kg) and children (300 mg q4w in patients 15–< 30 kg, 200 mg q2w in patients 30–< 60 kg) with moderate-to-severe AD.

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The Posology of Dupilumab in Pediatric Patients With Atopic Dermatitis

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