# Plasma proteomic profiles of patients with atopic dermatitis with moderate-to-severe pruritus treated with a single dose of nemolizumab

## TL;DR

This study explores how nemolizumab affects plasma proteins and immune pathways in patients with severe atopic dermatitis, revealing potential mechanisms behind its therapeutic effects.

## Contribution

The study identifies systemic immune pathways modulated by nemolizumab, offering new insights into its mechanism of action in atopic dermatitis.

## Key findings

- Nemolizumab modulates pathways like neutrophil degranulation and integrin signaling.
- It reverses disease-associated changes in key pathways, even with modest individual protein changes.
- TARC/CCL17 is linked to pruritus and eczema severity.

## Abstract

Nemolizumab demonstrates efficacy against pruritus and eczema by inhibiting IL-31 signaling in patients with atopic dermatitis. However, its effect on the systemic immune response at the molecular level remains unknown. In this study, we aimed to elucidate it by investigating plasma proteins and pathways modulated by nemolizumab under concomitant topical treatment. Plasma protein profiling was conducted for 25 Japanese patients with atopic dermatitis who received a single 60 mg dose of nemolizumab at baseline and 1, 2, 4, and 8 weeks after administration using the SomaScan 7k assay. Proteome data were analyzed through differential expression, linear regression, and enrichment analyses, which revealed upregulation of pathways such as neutrophil degranulation and integrin signaling, alongside downregulation of PTEN signaling. Although nemolizumab did not induce substantial changes at the individual protein level, it tended to reverse disease-associated alterations in many key pathways, as revealed by enrichment analysis using proteins with statistically significant but modest expression changes. In addition, we identified pathways and proteins—including TARC (thymus and activation-regulated chemokine)/CCL17—that were associated with pruritus and eczema severity. In conclusion, proteins and pathways involved in the systemic immune response modulated by nemolizumab were identified, potentially reflecting its therapeutic effects. The M525101-05 study (jRCT2080225290) was registered on July 22, 2020, and the MIT-502 study (jRCT1030230474) was registered on November 22, 2023.