Dupilumab Treatment for 16 Weeks Reported Mild Increases in Eosinophil Levels Without Clinical Relevance in Children Aged 6–11 Years with Severe Atopic Dermatitis

Background: In adult and adolescent patients with moderate-to-severe atopic dermatitis (AD), transient and clinically inconsequential increases in eosinophil counts were reported in previous 16-week phase 3 clinical trials of dupilumab. Here, we report the effect of dupilumab on eosinophil counts in children (aged 6–11 years) with severe AD in a phase 3 clinical trial.

Methods: In LIBERTY AD PEDS (NCT03345914; study approved by multiple institutional review boards: ICO1-17-448, 20172318), children were randomized 1:1:1 to dupilumab 100/200 mg every 2 weeks (q2w; loading dose 200/400 mg), 300 mg every 4 weeks (q4w; loading dose 600 mg), or placebo, with concomitant medium-potency topical corticosteroids (TCS). Mean eosinophil counts were evaluated at baseline and Weeks (Wks) 4/8/16.

Results: This analysis included 362 patients treated with dupilumab 100/200 mg q2w + TCS, dupilumab 300 mg q4w + TCS, or placebo + TCS. At baseline, mean eosinophil counts were elevated and similar in all groups (Table). Mean eosinophil counts increased over time, peaking at Wk 8 in the dupilumab 300 mg q4w + TCS and placebo + TCS groups, and a continued slight increase at Wk 16 in the dupilumab 100/200 mg q2w + TCS group (Table). Eosinophil counts > 5.0 × 10^9/L (grade 3 eosinophilia) were reported at ≥ 1 post-baseline timepoint in 2 patients treated with dupilumab 100/200 mg q2w + TCS, 5 patients treated with dupilumab 300 mg q4w + TCS, and 1 patient treated with placebo + TCS. Only 1 patient treated with dupilumab 100/200 mg q2w + TCS reported a treatment-emergent adverse event of eosinophilia (moderate eosinophilia) during the period when they had eosinophil counts > 5.0 × 10^9/L; this patient’s eosinophilia peaked at Wk 4 with incremental decreases at Wk 8 and 16 without treatment or intervention. No patients required treatment modification or withdrawal related to eosinophilia.

Conclusion: Children aged 6–11 years with severe AD treated with dupilumab 100/200 mg q2w + TCS or dupilumab 300 mg q4w + TCS experienced small and clinically inconsequential increases in mean eosinophils, consistent with previously published dupilumab laboratory safety data in adolescents and adults.

Presenting Author(s)

Amy S. Paller, MD
Chair, Department of Dermatology
Northwestern University Feinberg School of Medicine; Ann and Robert H. Lurie Children’s Hospital
Chicago, Illinois
Disclosure: AbbVie (Products/Services: Investigator, Consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Abeona Therapeutics (Products/Services: Consultant) (Consultant)Almirall (Products/Services: Consultant) (Consultant)AnaptysBio (Products/Services: Investigator) (Contracted Research (Principal Investigators must provide information, even if received by the institution))Asana BioSciences (Products/Services: Consultant) (Consultant)Boehringer Ingelheim (Products/Services: Consultant) (Consultant)BridgeBio Pharma (Products/Services: Consultant) (Consultant)Dermavant (Products/Services: Consultant) (Consultant)Dermira (Products/Services: Consultant) (Consultant)Eli Lilly (Products/Services: Investigator, consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Exicure (Products/Services: Consultant) (Consultant)Forté (Products/Services: Consultant) (Consultant)Galderma (Products/Services: Consultant) (Consultant)Incyte (Products/Services: Investigator, consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))InMed Pharmaceuticals (Products/Services: Consultant) (Consultant)Janssen (Products/Services: Consultant) (Consultant)Janssen (Products/Services: Investigator) (Contracted Research (Principal Investigators must provide information, even if received by the institution))LENUS Pharma (Products/Services: Investigator) (Contracted Research (Principal Investigators must provide information, even if received by the institution))LEO Pharma (Products/Services: Investigator, consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))LifeMax (Products/Services: Consultant) (Consultant)Novartis (Products/Services: Consultant) (Consultant)Novartis (Products/Services: Investigator) (Contracted Research (Principal Investigators must provide information, even if received by the institution))Pfizer (Products/Services: Consultant) (Consultant)RAPT Therapeutics (Products/Services: Consultant) (Consultant)Regeneron Pharmaceuticals, Inc. (Products/Services: Investigator, consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Sanofi Genzyme (Products/Services: Consultant) (Consultant)Sol-Gel (Products/Services: Consultant) (Consultant)UCB (Products/Services: Consultant) (Consultant)UCB (Products/Services: Investigator) (Contracted Research (Principal Investigators must provide information, even if received by the institution))

Co-Author(s)

AW
Andreas Wollenberg, Prof.
Head of the Dermatology and Allergy Unit
Ludwig-Maximilian University
Munich, Bayern, Germany
Disclosure: AbbVie (Products/Services: Consultant) (Consultant)Almirall (Products/Services: Consultant) (Consultant)Anacor Pharmaceuticals (Products/Services: Consultant) (Consultant)Beiersdorf (Products/Services: Investigator, research grant) (Grant/Research Support, Contracted Research (Principal Investigators must provide information, even if received by the institution))Eli Lilly (Products/Services: Investigator, consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Galapagos (Products/Services: Consultant) (Consultant)Galderma (Products/Services: Investigator, consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))LEO Pharma (Products/Services: Investigator, consultant, research grant) (Consultant, Grant/Research Support, Contracted Research (Principal Investigators must provide information, even if received by the institution))MedImmune (Products/Services: Investigator, consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Novartis (Products/Services: Investigator, consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Pfizer (Products/Services: Investigator, consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Pierre Fabre (Products/Services: Research grant) (Grant/Research Support)Regeneron Pharmaceuticals, Inc. (Products/Services: Investigator, consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Sanofi Genzyme (Products/Services: Investigator, consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))
MC
Michael Cork, Prof.
Head of Sheffield Dermatology Research in the Department of Infection
Sheffield Dermatology Research, University of Sheffield
Sheffield, England, United Kingdom
Disclosure: AbbVie (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Astellas Pharma (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Boots (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Dermavant (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Galapagos (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Galderma (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Hyphens Pharma (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Johnson & Johnson (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))L’Oréal (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))LEO Pharma (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Menlo Therapeutics (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Novartis (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Oxagen (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Pfizer (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Procter & Gamble (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Reckitt Benckiser (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Regeneron Pharmaceuticals, Inc. (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))Sanofi Genzyme (Products/Services: Investigator/consultant) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))
ES
Elaine Siegfried, Prof.
Professor of Pediatrics and Dermatology
Saint Louis University; Cardinal Glennon Children’s Hospital
St. Louis, Missouri
Disclosure: Dermavant (Products/Services: Consultant) (Consultant)Eli Lilly (Products/Services: Consultant, principle investigator in clinical trials) (Consultant, Contracted Research (Principal Investigators must provide information, even if received by the institution))GSK (Products/Services: Data and safety monitoring board member) (Consultant)Janssen (Products/Services: Principle investigator in clinical trials) (Contracted Research (Principal Investigators must provide information, even if received by the institution))LEO Pharma (Products/Services: data and safety monitoring board member) (Consultant)Novan (Products/Services: data and safety monitoring board member) (Consultant)Pfizer (Products/Services: Consultant) (Consultant)Regeneron Pharmaceuticals, Inc. (Products/Services: Consultant) (Consultant)Regeneron Pharmaceuticals, Inc. (Products/Services: Principle investigator in clinical trials) (Contracted Research (Principal Investigators must provide information, even if received by the institution))Stiefel (Products/Services: Principal Investigator in clinical trials) (Contracted Research (Principal Investigators must provide information, even if received by the institution))Verrica Pharmaceuticals (Products/Services: Principal Investigator in clinical trials) (Contracted Research (Principal Investigators must provide information, even if received by the institution))Verrica Pharmaceuticals (Products/Services: Consultant) (Consultant)
ZC
Zhen Chen, MD
Director, Medical Analytics
Regeneron Pharmaceuticals, Inc.
Tarrytown, New York
Disclosure: Regeneron Pharmaceuticals, Inc. (Products/Services: Employee and shareholder) (Employee, Stockholder/Ownership Interest (excluding diversified mutual funds))
FK
Faisal Khokhar, MD
Patient Safety Head
Regeneron Pharmaceuticals, Inc.
Tarrytown, New York
Disclosure: Regeneron Pharmaceuticals, Inc. (Products/Services: Employee and shareholder) (Employee, Stockholder/Ownership Interest (excluding diversified mutual funds))

Senior Author(s)

NL
Noah Levit, MD
Associate Medical Director, Medical Affairs Immunology
Regeneron Pharmaceuticals, Inc.
Tarrytown, New York
Disclosure: Regeneron Pharmaceuticals, Inc. (Products/Services: Employee and shareholder) (Employee, Stockholder/Ownership Interest (excluding diversified mutual funds))
AR
Ainara Rodriguez Marco, MD
Global Medical Director, Dermatology
Sanofi Genzyme
Madrid, Madrid, Spain
Disclosure: Sanofi Genzyme (Products/Services: Employee) (Employee)