Pruritus, atopic dermatitis gene expression downregulated by difelikefalin treatment
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BOSTON — Pruritus and atopic dermatitis-related gene expression were altered after treatment with difelikefalin, according to a study presented at the American Academy of Dermatology Annual Meeting.
“The results of this study highlight the promising effect of difelikefalin (DFK), a novel oral kappa opioid receptor agonist, for the treatment of moderate to severe pruritus in patients affected by atopic dermatitis,” Paola Facheris, MD, of the laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, told Healio. “Interestingly, we also saw an effect in the modulation of inflammation-related biomarkers in skin, suggesting that the interruption of the vicious itch-scratch cycle can possibly interfere with the inflammation cascade of atopic dermatitis.”
The phase 2 clinical study randomly assigned AD patients with moderate to severe pruritis 1:1:1:1 to receive twice-daily oral DFK at one of three different doses or placebo for 12 weeks. Forty subjects were included in a sub-study evaluating the effect of DFK on gene expression, measured by RNA-sequencing and TaqMan Low Density Array or reverse transcription polymerase chain reaction, using skin biopsies at baseline and week 12.
Downregulation of interleukin-31 and TRPV1, both pruritus-related genes, and the Th2 pathway was found in those treated with DFK.
“DFK can be a precious resource to treat moderate to severe pruritus for patients suffering from atopic dermatitis, providing relief to one of the most burdensome symptoms of the disease,” Facheris said. “In fact, clinicians are aware that severe pruritus in atopic dermatitis can heavily interfere with normal life causing sleep deprivation and leading to the onset of depressive symptoms among other consequences.”
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Facheris P, et al. Oral difelikefalin improves itch and inflammatory biomarkers in atopic dermatitis subjects with moderate to severe pruritus. Presented at: American Academy of Dermatology Annual Meeting; March 25-29, 2022; Boston.
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