Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis

摘要: Background Severe atopic dermatitis (AD) has a high unmet need for effective and safe therapeutics. In early-phase trials, dupilumab, fully human mAb targeting IL-4 receptor α, markedly improved disease activity, but the effect of IL-4/IL-13 blockade on AD at molecular level not been characterized. Objectives We sought to evaluate dupilumab modulation signature. Methods performed transcriptomic analyses pretreatment posttreatment skin biopsy specimens from patients with moderate-to-severe treated weekly 150 or 300 mg placebo. Results Exacerbation transcriptome was observed in placebo-treated patients. Dupilumab signature dose-dependent manner. Expression genes upregulated lesions decreased by 26% (95% CI, 21% 32%) 65% 60% 71%) treatment mg, respectively. Genes downregulated increased 16% 27%) 32% 37%) (150 respectively). The changes paralleled improvements clinical scores. A dupilumab 821 probes (>2-fold change, P K16 MKI67 ), T cells, dendritic cells ( CD1b CD1c ) potent inhibition H 2-associated chemokines CCL17 , CCL18 CCL22 CCL26 were noted without significant 1-associated (IFNG) . Conclusions This is first report showing rapid improvement targeted anti–IL-4 α therapy. These data suggest that IL-13 drive complex, 2-centered inflammatory axis AD.