Abstract Number: 67

Secukinumab treatment leads to proteomic and transcriptional changes in psoriatic skin

MA. Valentin, TR. Peters, E. Khokhlovich, X. Jiang,I. Koroleva, D. Lee, F. Sinner, T. Pieber, C. Dragatin,M. Bodenlenz, C. Loesche

Meeting: 2015 Dermcoll

Session Information

Date: -

Session Title: Poster Presentations

Session Time: -

Introduction and objectives: Secukinumab targets IL-17A
for the treatment of psoriasis. To gain insight into its mechanism
of action we investigated early changes in the transcriptional
and proteomic profiles in the epidermis (via tape
strips), dermis (interstitial fluid obtained by dermal open
flow microperfusion [dOFM]), and epidermis/dermis (via
biopsies) in subjects with psoriasis after a single subcutaneous
(s.c.) dose of secukinumab 300 mg.

Materials and methods: This study was conducted using
samples obtained from 8 subjects with moderate-to-severe
psoriasis plaques who received a single s.c. dose of
secukinumab on Day-1. Transcriptional data from lesional
biopsies at Baseline and Day 8 were obtained using
Affymetrix gene expression arrays, Nanostring nCounter
custom code sets, and qPCR. Using Aushon BioSystems’
multiplex biomarker platform, changes in 170 proteins
were evaluated in lesional skin using tape strips and
lesional and non-lesional interstitial fluid at Baseline and on
Day-8 after dosing with secukinumab.

Results: At 8 days after a single s.c. dose of secukinumab,
changes in gene expression were observed in mRNA and/or
protein levels of inflammatory cytokines and chemokines
(e.g., IL-1b, IL-17A, IL-17C, CXCL1, IL-8, IL-23/p19, IL-19,
IL-36 family members) as well as mediators affecting
keratinocyte proliferation (e.g., amphiregulin, epiregulin,
IL-22).

Conclusions: In this study we observed that key molecular
factors and processes implicated in psoriasis pathology
were already positively impacted by 8 days after a single
dose of secukinumab. The results support the role of IL-17A
in the pathogenesis of psoriasis and shed more light on the
rapid changes observed with novel anti–IL-17A therapies.