Orismilast, a Potent and Selective PDE4B/D Inhibitor, Reduces Protein Levels of Key Disease Driving Cytokines in the Skin of Patients With Plaque Psoriasis

Abstract

Minimally invasive sampling of the skin using tape strips for conducting biomarker research is a growing research area in medical dermatology. The goal of this study was to utilise tape strip sampling to investigate changes in protein skin levels of psoriasis patients after oral treatment with orismilast (a PDE4B/D inhibitor). The proteins were measured in extracts of tape-strip samples taken from the skin of patients with moderate–severe psoriasis participating in a 16-week Ph2b study (IASOS). The proteins were measured using the Olink technology or an ELISA assay. Our results show that protein levels of multiple proteins (32/71) were upregulated at baseline in the lesional skin compared to non-lesional skin, including three key biomarkers of the psoriasis disease pathology (IL-17A, CCL20 and TNFα). The protein levels of these three biomarkers were significantly reduced at Week 16, reaching a percent reduction of 52% and 51% for IL-17A, 66% and 60% for TNFα, and 41% and 54% for CCL20 for the two doses analysed (20 and 30 mg bid, respectively). In addition, we observed that the clinical response of a 75% reduction in PASI (PASI75) was associated with a 98% reduction in IL-17A protein levels in lesional skin, irrespective of the orismilast dose. In summary, a significant reduction of key proteins related to the T_H17 axis and T_H1 axis was observed in the skin of psoriasis patients after treatment with oral orismilast, supporting the observed clinical effect. Finally, this constitutes the first report where protein levels from the skin of psoriasis patients are quantified using tape strips as a minimally invasive skin sampling technology in combination with the Olink technology.

Trial Registration: ClinicalTrials.gov identifier: NCT05190419