Dupilumab

Dupilumab (REGN-668) is a fully human mAb to IL-4 receptor α (IL-4Rα) that inhibits both IL-4 and IL-13 signaling, markedly improved moderate-to-severe atopic dermatitis[1].

Dupilumab suppressed mRNA expressions of genes related to activation of T cells, DCs, eosinophils, inflammatory pathways, and TH2-inducing chemokines in skin lesions. No significant reduction in IL-17A or IL-22 levels is detected, but large reductions in expression of IL-17-related genes, such as elafin (PI3), IL23p19/IL23A, and S100A8 and trends for suppression (CXCL1 and S100A7) are found with 300 mg of Dupilumab[1]. Major suppressions of hyperplasia-related genes (eg, K16) and reductions in expression of S100A genes are evident with 300 mg of Dupilumab by using microarrays and qRT-PCR. The changes in other critical epidermal alterations in severe atopic dermatitis (AD) skin are also measured, including significant increases in claudin and lipid product levels with 300 mg of Dupilumab. A trend of dose-dependent increases in expression of differentiation genes (LOR and FLG) is observed after adjusting for suppression of epidermal hyperplasia, as demonstrated by K16 reductions with Dupilumab[1].

[1]. Hamilton JD, et al. Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2014 Dec;134(6):1293-1300.