Blood transcriptome signature as indicator and predictor for efficacy of abrocitinib in treatment of atopic dermatitis.

Abstract

Atopic dermatitis (AD) patients exhibit significant blood transcriptome alterations, reflecting systemic inflammation. The effects of abrocitinib, a Janus kinase 1 inhibitor, on the blood transcriptome of AD remain unclear. This study aim to investigate abrocitinib's effects on the blood transcriptome in AD patients and identify transcriptomic predictors of treatment efficacy. Blood cell mRNA sequencing was conducted on 31 AD patients at baseline, 4, and 12 weeks of 100 mg abrocitinib daily treatment. Differential gene expression, immune infiltration, and weighted gene co-expression network analyses (WGCNA) were performed, along with correlation analysis of transcriptomic data and clinical traits. We observed that abrocitinib treatment significantly improved clinical signs of AD. Correspondingly, blood transcriptome normalization, including downregulation of Th2, Th1, eosinophil, and an increase in Tr1 cell abundance, rapidly occurred by week 4, with slight rebound by week 12. Higher baseline eosinophil counts predicted greater transcript normalization. WGCNA identified an efficacy-related gene module, leading to a five-gene (PLIN2, CAT, CLC, RAB44, SMPD3) efficacy-predictive model, which was validated in another independent cohort of 30 AD patients treated with abrocitinib. In conclusion, abrocitinib treatment resulted in rapid and extensive normalization of the dysregulated blood transcripts in AD, which was associated with its clinical efficacy.