Dupilumab improved molecular signature in patients with atopic dermatitis

Data from a study published in the Journal of Allergy and Clinical Immunology demonstrate dupilumab was associated with a dose-dependent improvement in atopic dermatitis transcriptome compared with placebo.

“In this study, statistically significant, dose-dependent improvements of the atopic dermatitis [AD] transcriptome were observed in patients treated with 4 weeks of dupilumab compared with placebo,” researchers wrote.

Researchers obtained skin biopsies from 18 adult patients with moderate-to-severe chronic AD who were part of two phase 1 studies. In the current study, researchers aimed to determine the effect of dupilumab (Regeneron Pharmaceuticals Inc. and Sanofi), an anti-IL4 receptor alpha therapy, on AD molecular signature. The studies were multicenter, randomized, double-blind and placebo-controlled trials of weekly subcutaneous injections of 150 mg or 300 mg of dupilumab or placebo for 4 weeks.

Using lesional skin biopsy specimens, the researchers reported dose-dependent changes in upregulated genes: -26% among patients assigned to 150 mg dupilumab and -65% among those assigned to 300 mg dupilumab. Changes were also observed in downregulated genes: +32% in the 150-mg group and +21% in the 300-mg group. Molecular changes correlated with improved clinical scores.

Study results also showed Eczema Area and Severity Index scores improved at least 50% from baseline in all but one patient assigned to 300 mg of dupilumab vs. none of the patients assigned to placebo, according to researchers.

“These results suggest that inhibition of a single target has the potential to reverse AD pathomechanisms, opening the door to a new era of targeted treatment for this common and debilitating inflammatory skin disease,” researchers wrote.

Disclosure: See the study for a full list of all authors’ relevant financial disclosures.

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Source:

Hamilton JD. J Allergy Clin Immunol. 2014;134:1293-1300.