Dupilumab reduces inflammatory biomarkers in pediatric patients with moderate-to-severe atopic dermatitis.

atopic dermatitis biomarkers dupilumab inflammation pediatric

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
21 Aug 2024
Historique:
received: 25 10 2023
revised: 14 08 2024
accepted: 15 08 2024
medline: 24 8 2024
pubmed: 24 8 2024
entrez: 23 8 2024
Statut: aheadofprint

Résumé

Patients with atopic dermatitis (AD) often have elevated type 2 inflammatory serum biomarkers. To report changes in thymus- and activation-regulated chemokine (TARC)/CC chemokine ligand 17 (CCL17), total immunoglobulin E (IgE), lactate dehydrogenase (LDH), and eosinophils in pediatric patients treated with dupilumab or placebo. Biomarker data were analyzed from three randomized, double-blind, placebo-controlled, phase 3 studies of patients with moderate-to-severe AD. Patients aged 6 months-5 years were randomized to weight-dependent dupilumab 200/300mg every 4 weeks (q4w) or placebo; aged 6-11 years to dupilumab 100/200mg every 2 weeks (q2w), dupilumab 300mg q4w, or placebo; aged 12-17 years to dupilumab 200/300mg q2w, dupilumab 300mg q4w, or placebo. The youngest two groups also applied topical corticosteroids. Median percent changes from baseline to week 16 reported using last observation carried forward method, censoring after rescue treatment. Pediatric patients who received dupilumab vs placebo achieved significantly greater median percent reductions at week 16 in: TARC/CCL17 (-83.3% to -72.4% vs -14.9% to -1.8%), total IgE (-71.2% to -58.4% vs -21.0% to +28.1%), and LDH (-26.2% to -9.8% vs -1.5% to +1.5%). All comparisons were significantly different (P < .0001) between each dupilumab dosing group and respective placebo groups. In contrast, absolute changes in eosinophils were small in all groups. Dupilumab treatment for pediatric patients with moderate-to-severe AD significantly reduced levels of TARC/CCL17, total IgE, and LDH to levels comparable to those of healthy controls, reflecting a reduction in systemic type 2 and general inflammation.

Sections du résumé

BACKGROUND BACKGROUND
Patients with atopic dermatitis (AD) often have elevated type 2 inflammatory serum biomarkers.
OBJECTIVE OBJECTIVE
To report changes in thymus- and activation-regulated chemokine (TARC)/CC chemokine ligand 17 (CCL17), total immunoglobulin E (IgE), lactate dehydrogenase (LDH), and eosinophils in pediatric patients treated with dupilumab or placebo.
METHODS METHODS
Biomarker data were analyzed from three randomized, double-blind, placebo-controlled, phase 3 studies of patients with moderate-to-severe AD. Patients aged 6 months-5 years were randomized to weight-dependent dupilumab 200/300mg every 4 weeks (q4w) or placebo; aged 6-11 years to dupilumab 100/200mg every 2 weeks (q2w), dupilumab 300mg q4w, or placebo; aged 12-17 years to dupilumab 200/300mg q2w, dupilumab 300mg q4w, or placebo. The youngest two groups also applied topical corticosteroids. Median percent changes from baseline to week 16 reported using last observation carried forward method, censoring after rescue treatment.
RESULTS RESULTS
Pediatric patients who received dupilumab vs placebo achieved significantly greater median percent reductions at week 16 in: TARC/CCL17 (-83.3% to -72.4% vs -14.9% to -1.8%), total IgE (-71.2% to -58.4% vs -21.0% to +28.1%), and LDH (-26.2% to -9.8% vs -1.5% to +1.5%). All comparisons were significantly different (P < .0001) between each dupilumab dosing group and respective placebo groups. In contrast, absolute changes in eosinophils were small in all groups.
CONCLUSIONS CONCLUSIONS
Dupilumab treatment for pediatric patients with moderate-to-severe AD significantly reduced levels of TARC/CCL17, total IgE, and LDH to levels comparable to those of healthy controls, reflecting a reduction in systemic type 2 and general inflammation.

Identifiants

pubmed: 39178993
pii: S0091-6749(24)00826-1
doi: 10.1016/j.jaci.2024.08.005
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Lisa A Beck (LA)

Department of Dermatology, University of Rochester Medical Center, Rochester, NY, USA. Electronic address: lisa_beck@urmc.rochester.edu.

Antonella Muraro (A)

Food Allergy Referral Centre, Padua University Hospital, Padua, Italy.

Mark Boguniewicz (M)

Division of Allergy-Immunology, Department of Pediatrics, National Jewish Health, Denver, CO, USA; University of Colorado School of Medicine, Denver, CO, USA.

Zhen Chen (Z)

Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA.

Joseph Zahn (J)

Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA.

Ainara Rodríguez Marco (AR)

Sanofi, Madrid, Spain.

Classifications MeSH