Metabolomic Signature Predictive of Ocular Side Effects in Dupilumab-Treated AD: Study

Key Takeaways

• Dupilumab-treated AD patients who develop ocular side effects show distinct metabolic signatures at baseline, according to this study.

• Benzoate and tyrosine metabolism pathways, along with specific lipid alterations, were enriched in the DAOSD group.

• Metabolomics may help predict DAOSD risk, potentially improving clinical monitoring and treatment selection.

New research suggests baseline metabolic differences may help predict which patients with atopic dermatitis (AD) are most likely to develop ocular complications from dupilumab.

In findings published in JID Innovations, researchers used mass spectrometry-based metabolomics and lipidomics to evaluate plasma and serum from adult AD patients treated with dupilumab. Among 20 participants, six developed dupilumab-associated ocular surface disease (DAOSD), a term encompassing conjunctivitis, keratitis, and other ocular conditions that have been reported in up to 60% of AD patients treated with the drug.

Researchers for the prospective cohort study collected longitudinal samples at baseline, 4 weeks, 16 weeks, and the time of DAOSD onset. Using multivariate analyses, the team identified metabolomic and lipidomic patterns distinguishing patients who would later develop ocular side effects. Key metabolic pathways benzoate and tyrosine metabolism.

DAOSD cases changed over time compared to controls, showing increased citrulline biosynthesis and proline metabolism activity. These observations point toward possible microbial-host interactions or barrier dysfunctions contributing to DAOSD susceptibility, the authors said.

“We show that the plasma metabolome can distinguish patients who develop DAOSD from those who do not,” the authors wrote in the study. “Metabolomic signatures may be used to identify patients at risk for DAOSD prior to treatment.”

The small sample size and single-center design were cited as limitations. The authors maintained the metabolomic findings represent a promising step toward predictive biomarkers, and that the data could help guide risk stratification and preemptive management strategies as dupilumab use becomes more widespread.

Source: Patra D, He H, Lee D, et al. Metabolomic and lipidomic profiling identify signatures in atopic dermatitis patients with dupilumab-associated ocular surface disease.JID Innov. 2025. doi:10.1016/j.xjidi.2024.100185