Molecular profile of interleukin-17RA blockade by brodalumab in Japanese patients with psoriasis: Results from the ESPRIT study

Abstract

Background

Brodalumab, an anti-interleukin-17 receptor A antibody, is effective in psoriasis via action on the IL-17 pathway.

Objective

This analysis of an exploratory intervention study (ESPRIT) in Japanese patients with moderate to severe plaque psoriasis examined the brodalumab efficacy by clinical changes, and modulation of skin inflammation via changes in skin gene expression and blood sample protein expression.

Methods

Primary clinical endpoints were changes in PASI score and PASI score 0 achievement rate at Week 12. For molecular endpoints, biopsies of lesional, non-lesional and healthy volunteer skin were examined by RNA sequencing and RT-PCR. Blood sample serum was analyzed by Olink high-throughput proteomics.

Results

Twenty healthy volunteers and 40 patients were enrolled; 37 underwent molecular profiling. Clinical assessment showed that the median baseline PASI score (19.0) significantly decreased to 0.4 at Week 12 (P < 0.0001), with more rapid decline in higher PASI responders. Molecular assessment demonstrated that differential expressed genes in lesional skin were suppressed equivalently to non-lesional skin, establishing the molecular improvement with brodalumab. The transcriptomes of Japanese and Western patients were similar, and top-upregulated genes included IL-17-inducible and cardiovascular disease-related genes, which were suppressed by brodalumab. Serum protein analysis identified 22 proteins elevated by psoriasis. Several inflammatory and cardiovascular risk proteins correlated with psoriasis severity and BMI, but at lower rates than in Western patients.

Conclusions

In summary, the transcriptome and the proteome characteristics of Japanese and Western psoriasis patients were similar. Brodalumab rapidly improved skin and serum molecular levels and reduced cardiovascular disease risk factor expression.