Dupilumab Shifts Skin Microbiome Toward Control Levels

Dupilumab is efficacious in restoring a healthy skin microbiome in patients with moderate-to-severe atopic dermatitis.

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In a recent study,¹ researchers sought to determine the efficacy of both dupilumab and cyclosporine in restoring the skin biome. Additionally, they investigated the associations between atopic dermatitis and the skin microbiome, clinical data, and responses to systemic therapies.

According to the study, patients with atopic dermatitis possess an altered skin microbiome, which can either be indicative of or drive inflammation.

Study participants (n=415) were adults with moderate-to-severe atopic dermatitis who were listed on the TREATgermany registry. Researchers recruited prospective participants from August 2017 to March 2019. The study was divided into 2 parts, including an optional bioanalytics portion and the overall trial portion. Before receiving treatment, all participants were required to avoid bathing, showering, or topical applications at least 24 hours prior.

Researchers collected anticubital skin swabs from 157 participants prior to the start of the study and at the 3 month mark in order to collect demographic data, including history of systemic treatment, previous treatment with cyclosporine, and disease severity. Disease severity was measured by the Eczema Area and Severity Index (EASI) and the Objective SCORing of Atopic Dermatitis (oSCORAD) scale.

130 participants were treated with dupilumab, 27 participants were treated with cyclosporine, and 258 participants were considered controls. Control group participants were considered healthy in nature and did not have a history of atopic or chronic inflammatory disease. In the control group, researchers sampled, extracted, and processed antecubital fossa skin swabs involving 16S rRNA sequence data, again at baseline and at 3 months.

Researchers considered treatment response to be a minimum 75% EASI score improvement after 3 months of therapy. Nonresponse was defined as not reaching a minimum 50% EASI score improvement by the same benchmark.

By the conclusion of the study, researchers found that participants with atopic dermatitis had skin microbiomes characterized by lower diversity and higher rates of Staphylococcus genus and S. aureus than that of participants in the control group. Furthermore, they also noted that alpha diversity and S. aureus were significantly linked to baseline severity of disease.

In participants being treated with dupilumab, bacterial diversity shifted closer to a healthy or control state. However, this was not the case in patients treated with cyclosporine. Additionally, dupilumab decreased S. aureus, whereas cyclosporine did not.

In patients who had achieved an EASI score of 90 as a result of dupilumab therapy, researchers cited few differences in microbial diversity when compared to healthy individuals after 3 months of treatment.

Limitations of the study included its lack of randomization and control in a real-world setting, in addition to smaller sample group sizes.

“Our observations from this large real-world observational study confirm and extend previous findings on skin microbiome restoration associated with targeted type-2 cytokine blockade, which appears to be at least in part caused by direct drug effects beyond improvements of inflammation and clinical scores,” study authors wrote. “Future studies should examine the overlapping and individual effects of IL-4 and IL-13 signaling as well as their blockade on cutaneous microbiota and the host antimicrobial response to assess the mechanism responsible for the improvement in the microbiome with treatment.”

Reference

1. Hartmann J, Moitinho‐Silva L, Sander N, et al. Dupilumab but not cyclosporine treatment shifts the microbiome towards a healthy skin flora in patients with moderate to severe atopic dermatitis. Allergy. 2023. doi:10.1111/all.15742