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

Abstract

Background: Patients with atopic dermatitis (AD) often have elevated type 2 inflammatory serum biomarkers.

Objective: The aim was to report changes in thymus and activation-regulated chemokine (TARC)/CC chemokine ligand 17 (CCL17), total IgE, lactate dehydrogenase (LDH), and eosinophils in pediatric patients treated with dupilumab or placebo.

Methods: Biomarker data were analyzed from 3 randomized, double-blind, placebo-controlled, phase 3 studies of patients with moderate-to-severe AD. Patients ages 6 months to 5 years were randomly assigned to weight-dependent dupilumab 200/300 mg every 4 weeks (q4w) or placebo; ages 6 to 11 years, to dupilumab 100/200 mg every 2 weeks (q2w), dupilumab 300 mg q4w, or placebo; ages 12 to 17 years, to dupilumab 200/300 mg q2w, dupilumab 300 mg q4w, or placebo. In the youngest 2 groups, topical corticosteroids were also applied. Median percent changes from baseline to week 16 were reported using last observation carried forward analysis, censoring after rescue treatment.

Results: Pediatric patients who received dupilumab versus 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: Dupilumab treatment for pediatric patients with moderate-to-severe AD significantly reduced levels of TARC/CCL17, total IgE, and LDH to levels comparable with those of healthy controls, reflecting a reduction in systemic type 2 and general inflammation.

Keywords: Atopic dermatitis; biomarkers; dupilumab; inflammation; pediatric.