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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U2 - 10.1002/cpt.2366
DO - 10.1002/cpt.2366
M3 - Article
C2 - 34270797
AN - SCOPUS:85113762848
SN - 0009-9236
VL - 110
SP - 1318
EP - 1328
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 5
ER -