TOPLINE

Treatment with abrocitinib, a JAK-1 selective inhibitor, was associated with favorable changes in the skin microbiome, most notably a reduction in Staphylococcus aureus abundance and increased skin microbial diversity, in patients with moderate-to-severe atopic dermatitis (AD).

METHODOLOGY

• Researchers evaluated data from a phase 2a trial involving 43 patients with moderate-to-severe AD in the US who had an inadequate response to topical medications or required systemic therapy and were randomly assigned to receive 200 mg abrocitinib, 100 mg abrocitinib, or placebo once daily for 12 weeks.
• Skin swabs were collected from lesional skin at baseline and 2, 4, and 12 weeks and from nonlesional skin at baseline and 4 and 12 weeks; the samples collected were then analyzed using 16S rRNA gene amplicon sequencing to determine microbial composition.
• Assessments included the analysis of the effect of abrocitinib treatment on microbial alpha- and beta-diversity and on the abundance of Staphylococcus and S aureus over the treatment period.
• Whether changes in the skin microbiome following abrocitinib treatment correlated with improvements in clinical metrics and favorable changes in the expression of inflammatory and skin barrier markers were also assessed.

TAKEAWAY

• Staphylococcus abundance decreased significantly in lesional skin with 200 mg abrocitinib from baseline to 12 weeks (false discovery rate [FDR] < .05), whereas S aureus abundance decreased with abrocitinib vs placebo at 2, 4, and 12 weeks in lesional skin and at 4 weeks in nonlesional skin (FDR < .01).
• Alpha-diversity increased significantly with 200 mg abrocitinib from baseline to 12 weeks in both lesional and nonlesional skin (P < .05).
• Beta-diversity differed significantly between the abrocitinib and placebo groups as early as 2 weeks in lesional skin, with the difference persisting through 12 weeks (P ≤ .05).
• Abrocitinib treatment was associated with dose-dependent reductions in AD signs and symptoms compared with placebo treatment as early as 2 weeks, with effects sustained through 12 weeks.

IN PRACTICE

“This study adds to the body of evidence indicating that targeting inflammatory pathways improves microbiome dysregulation in the skin of patients with AD,” the authors wrote. “Immunomodulatory effects of abrocitinib may be associated with changes in the AD skin microbiome, notably increased microbial diversity and decreased Staphylococcus and S aureus abundance, thereby altering a core component of the disease pathophysiology,” they added.

SOURCE

Emma Guttman-Yassky, MD, PhD, with the Icahn School of Medicine at Mount Sinai, New York City, was the corresponding author of the study, which was published online on August 2 in Allergy.

LIMITATIONS

Sample sizes were relatively small, contributing to imbalances in baseline demographic characteristics and disease severity, including a significant difference in sex distribution, between treatment groups despite randomization.

DISCLOSURES

This study was supported by Pfizer Inc. Several authors were employees and shareholders of the company. The corresponding author reported serving as an advisory board member, consultant, and/or investigator for numerous pharmaceutical companies, including Pfizer Inc.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.