Nemolizumab, an investigational monoclonal antibody that blocks signaling from IL-31, is currently being evaluated for treatment of atopic dermatitis (AD). IL-31 plays a key role in all major aspects of AD pathophysiology (pruritus, inflammation and skin barrier dysfunction). However, the molecular and cellular responses resulting from blocking IL-31 signaling in AD are less understood.
Plasma samples (n=132) were collected at 3 time points (baseline, week 4 and week 16) from 44 subjects with moderate-to-severe AD who were randomized (23 placebo, 21 nemolizumab) in a Nemolizumab Phase 2b study (NCT03100344). At each time point, disease severity was quantified with the Eczema Area and Severity Index (EASI). Protein expression in the plasma was measured with SomaScan (Somalogic). We identified 254 disease-associated proteins (‘EASI-signature’) in the plasma by correlating protein expression with disease severity. RFX5, which regulates the expression of MHC-II and T cell activation, had the most significant (positive) correlation with EASI. An enrichment analysis of the EASI-signature pointed out ‘Dermatitis’ and ‘Immune Mediated Inflammatory Disease’ as most strongly associated disease terms. From the same dataset, we identified 13 proteins (‘NEMO-signature’) whose response, either at week 4 or 16, in the nemolizumab-treated group significantly differed from response in the placebo group. The NEMO-signature contains proteins regulating skin barrier (COL5A1), inflammation (S100A4), T-cell activation (RFX5) and axon development (GLDN). The signature is also enriched with cell adhesion proteins, suggesting an additional impact of nemolizumab in inflammatory cell infiltration. Of note, 2 proteins of the NEMO-signature (RFX5, S100A4) are part of the EASI-signature, thereby connecting nemolizumab effects to improvements in disease severity.
Our findings reinforce the immune aspect of AD pathophysiology and indicate that nemolizumab may decrease AD severity by impacting hallmark processes of AD.

LB056 - Plasma proteome signatures that correlate with disease severity and nemolizumab treatment

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.