Effect of Abrocitinib on the Skin Microbiome in Patients With Moderate-to-Severe Atopic Dermatitis

Abstract

Background

Atopic dermatitis (AD) is characterized by microbial dysbiosis, notably an overabundance of Staphylococcus species. This study aimed to evaluate the effects of abrocitinib, a Janus kinase 1-selective inhibitor, on the skin microbiome and clinical outcomes in patients with moderate-to-severe AD.

Methods

Patients enrolled in JADE MOA (NCT03915496) were randomly assigned to receive once-daily abrocitinib (100 or 200 mg) or placebo for 12 weeks. Skin swabs collected at baseline and Weeks 2, 4, and 12 underwent 16S rRNA gene amplicon sequencing to determine microbial composition. Disease severity was assessed at the same time points using established clinical metrics. Associations between microbial abundance and clinical metrics, as well as inflammatory and skin barrier markers, were investigated.

Results

Data from 43 patients were included. Alpha diversity increased significantly at Week 12 of treatment with abrocitinib 200 mg. Beta diversity analysis revealed clustering of the abrocitinib groups away from placebo as early as Week 2; divergence continued through Week 12. Staphylococcus and S. aureus relative abundance decreased in a dose-dependent manner from Week 2 through Week 12 of abrocitinib treatment. Changes in skin microbial composition corresponded with improvements in clinical metrics of disease severity as well as immune markers of AD.

Conclusions

Abrocitinib treatment is associated with beneficial changes in the skin microbiome, notably a reduction in S. aureus and increased microbial diversity. These findings provide insight into the mechanism of action of abrocitinib and the interplay of immunomodulation and the skin microbiome in AD.

Trial Registration

ClinicalTrials.gov identifier: NCT03915496