Blood Transcriptome Signature as Indicator and Predictor for Efficacy of Abrocitinib in Treatment of Atopic Dermatitis

Abstract

Patients with atopic dermatitis (AD) exhibit significant blood transcriptome alterations, reflecting systemic inflammation. The effects of abrocitinib, a Jak1 inhibitor, on the blood transcriptome of AD remain unclear. This study aimed to investigate abrocitinib’s effects on the blood transcriptome in patients with AD and identify transcriptomic predictors of treatment efficacy. Blood cell mRNA sequencing was conducted on 31 patients with AD at baseline and 4 and 12 weeks of 100 mg abrocitinib daily treatment. Differential gene expression, immune infiltration, and weighted gene coexpression network analyses 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 T helper 2, T helper 1, and eosinophil and an increase in type 1 regulatory T-cell abundance, rapidly occurred by week 4, with slight rebound by week 12. Higher baseline eosinophil counts predicted greater transcript normalization. Weighted gene coexpression network analyses identified an efficacy-related gene module, leading to a 5-gene (PLIN2, CAT, CLC, RAB44, and SMPD3) efficacy-predictive model, which was validated in another independent cohort of 30 patients with AD 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.