Highlights from

WCD 2019

World Congress of Dermatology

Milan 10-15 June 2019

Topical PD4 inhibitor acts by reduction of proinflammatory cytokines

An intra-patient, controlled, phase 2 study shed light on the mode of action of the phosphodiesterase inhibitor crisaborole in atopic dermatitis (AD). Hand in hand with clinical improvement, crisaborole reduces the expression of key proinflammatory cytokines in the AD pathogenesis.

The topical PDE4 inhibitor crisaborole is a novel non-steroidal treatment for mild-to-moderate AD. In 2016, it was FDA approved due to the positive results of two phase 2 trials including more than 1,500 patients. However, its mode of action is not well understood. A phase 2 trial presented during the WCD 2019 assessed the relationship between clinical improvement with crisaborole and changes in skin hyperplasia, barrier function, and immune biomarkers. Patients with mild-to-moderate AD (n=40) were treated for 15 days, after which punch biopsies were processed for gene expression studies and immunohistochemistry.

After 15 days, greater improvement from baseline was observed for crisaborole-treated lesions than for vehicle-treated lesions in total sign score (TSS) and pruritus on a numerical rating scale. Pruritus started to improve after only 1 day of treatment. Transepidermal water loss improved significantly after a treatment period of 8 days.

In addition, skin biopsies at day 15 showed a reduction compared with baseline in expression of biomarkers associated with general inflammation (Matrix Metalloproteinase 12 expression), as well as biomarkers of the Th2 and Th17/Th22 axes, which play a key role in AD pathogenesis. Evaluation of the immunohistochemistry showed that epidermal hyperplasia and immune cell infiltration was improved in lesional skin after crisaborole treatment compared with baseline. The authors conclude that crisaborole improved the AD lesional transcriptome profile towards non-lesional skin. Both molecular and cellular changes were positively correlated with clinical improvement of AD.

  1. Guttman-Yassky E, et al. Changes in skin biomarkers following crisaborole treatment correlate with clinical improvement in atopic dermatitis. Poster presented at the World Congress of Dermatology 2019, 10-15 June, Milan, Italy.

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