Proteomic investigation of the effect of PDE4 inhibitor on Atopic Dermatitis

Abstract

Atopic Dermatitis (AD) is a common inflammatory skin disease characterized by the development of chronic or relapsing eczematous lesions. A phase III clinical trial study has shown that patients with mild to moderate AD who were treated with Crisaborole ointment experienced rapid and clinically relevant improvement. Crisaborole is a nonsteroidal phosphodiesterase 4 (PDE4) inhibitor. Clinical studies have shown that Crisaborole is effective and has a low incidence of treatment-related and treatment-emergent adverse events in patients with mild-to-moderate AD.

This study used the technique of tape stripping (TS) sample collection coupled with proteomics and extensive bioinformatics analysis that allows an understanding of the proteomic differences between TS samples of AD collected before and after treatment with the PDE4 inhibitor, Crisaborole, and control groups. This study aims to discover the effect of Crisaborole on adaptive immunity, inflammation, skin barrier and repair on AD, and potentially investigate and identify alternative or complementary mechanism of actions of Crisaborole.

This study showed that tape stripping was able to find the proteomic changes between NS, UAD and TAD after the use of Crisaborole after 45 days. The proteins found has shown that there’s a link between AD and the PDE4 pathways with the proteomic changes in the use of Crisaborole on AD skin. The effect of Crisaborole on AD showed that inflammatory pathways, mediators and cytokines were inhibited. Furthermore, there’s improvement of the skin barrier that activates the expression of keratinocytes differentiation molecules such as filaggrin, loricrin, and involucrin. Additionally, there’s a decrease in disease severity, supresses itch, clinical symptoms of AD and skin lesions.