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The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

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

Open access
Hamilton, Jennifer D., Suárez-Fariñas, Mayte, Dhingra, Nikhil, Cardinale, Irma, Li, Xuan, Kostic, Ana, Ming, Jeffrey E., Radin, Allen R., Krueger, James G., Graham, Neil, Yancopoulos, George D., Pirozzi, Gianluca, Guttman-Yassky, Emma·2014·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2014.10.013
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Abstract

BACKGROUND: Severe atopic dermatitis (AD) has a high unmet need for effective and safe therapeutics. In early-phase trials, dupilumab, a fully human mAb targeting IL-4 receptor α, markedly improved disease activity, but the effect of IL-4/IL-13 blockade on AD at the molecular level has not been characterized. OBJECTIVES: We sought to evaluate dupilumab modulation of the AD molecular signature. METHODS: We performed transcriptomic analyses of pretreatment and posttreatment skin biopsy specimens from patients with moderate-to-severe AD treated weekly with 150 or 300 mg of dupilumab or placebo. RESULTS: Exacerbation of the AD transcriptome was observed in placebo-treated patients. Dupilumab improved the AD signature in a dose-dependent manner. Expression of genes upregulated in AD lesions decreased in patients treated with dupilumab by 26% (95% CI, 21% to 32%) and 65% (95% CI, 60% to 71%) for treatment with 150 and 300 mg, respectively. Genes downregulated in AD lesions increased by 21% (95% CI, 16% to 27%) and 32% (95% CI, 26% to 37%) with dupilumab (150 and 300 mg, respectively). The molecular changes paralleled improvements in clinical scores. A dupilumab treatment signature of 821 probes (>2-fold change, P < .05) significantly modulated in the 300-mg dupilumab group at week 4 compared with baseline was identified in this sample set. Significant (P < .05) decreases in mRNA expression of genes related to hyperplasia (K16 and MKI67), T cells, and dendritic cells (CD1b and CD1c) and potent inhibition of TH2-associated chemokines (CCL17, CCL18, CCL22, and CCL26) were noted without significant modulation of TH1-associated genes (IFNG). CONCLUSIONS: This is the first report showing rapid improvement of the AD molecular signature with targeted anti-IL-4 receptor α therapy. These data suggest that IL-4 and IL-13 drive a complex, TH2-centered inflammatory axis in patients with AD.

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Metadata

Authors
Hamilton, J. D., Suárez-Fariñas, M., Dhingra, N., Cardinale, I., Li, X., Kostic, A., Ming, J. E., Radin, A. R., Krueger, J. G., Graham, N., Yancopoulos, G. D., Pirozzi, G., & Guttman-Yassky, E.
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2014-12
Volume
134
Issue
6
Pages
1293-1300
ISSN
0091-6749 (ISSN-L)
DOI
10.1016/j.jaci.2014.10.013
OpenAlex
W2012868073
Cited by
469
References
39
FWCI
34.99
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. https://app.cochat.ai/papers/10.1016/j.jaci.2014.10.013
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Hamilton, J. D., Suárez-Fariñas, M., Dhingra, N., Cardinale, I., Li, X., Kostic, A., Ming, J. E., Radin, A. R., Krueger, J. G., Graham, N., Yancopoulos, G. D., Pirozzi, G., & Guttman-Yassky, E. (2014). Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2014.10.013

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