Monoclonal Antibodies for Restoring a Healthy Skin Microbiome in Atopic Dermatitis Patients

In a 2023 study by Hartmann et al., a 3-month treatment regimen with dupilumab was found in patients with AD to produce a notable shift toward a skin microbiome composition resembling that of individuals without AD.¹ Notably, patients who received the same duration of treatment with cyclosporine did not exhibit comparable positive changes in their skin microbiomes.

Background and Study Results

It has been well-established in previous studies that AD is associated with decreased diversity of skin microbiota.² The skin microbiome in AD is classically characterized by an overgrowth of Staphylococcus aureus, and previous studies have also shown increased colonization with S. aureus to be associated with flare-ups and higher disease severity.²

Dupilumab is an anti-IL-4 R alpha antibody commonly used in the treatment of moderate-to-severe atopic dermatitis.¹ Interestingly, a previous 2020 study by Callewaert et al. found that treatment with dupilumab was correlated with not only clinical improvement of AD symptoms but also with decreased abundance of S. aureus and enhanced skin microbiome diversity in patients with AD.³In this 2023 study by Hartmann et al., researchers in Germany aimed to further characterize the direct effect of IL-4RA-blockade on the skin microbiome by comparing the skin microbiomes of AD patients being treated with dupilumab with the skin microbiomes of AD patients being treated with the calcineurin inhibitor cyclosporine.

Hartmann et al.’s study included a total of 157 participants, with 130 of these participants receiving treatment with dupilumab and 27 receiving treatment with cyclosporine. Antecubital skin swabs were collected from these 157 participants before treatment and after 3 months of treatment with either dupilumab or cyclosporine. Microbiome data from these 157 participants was compared with microbiome data from 258 population-based healthy controls (adults without skin or allergic diseases). Disease severity was also evaluated before and after treatment using the Eczema Area and Severity Index (EASI) and Objective SCORing of Atopic Dermatitis (oSCORAD) measures.

After 3 months, treatment with dupilumab was found to be associated with an increase in overall microbial diversity, a decrease in S. aureus colonization, and an increase in S. hominis in both lesional and nonlesional skin (although these changes were observed to a lesser degree than in lesional skin).¹ However, these positive changes in the skin microbiome were not observed in patients who received the same duration of treatment with cyclosporine. Interestingly, dupilumab was found to shift the skin microbiome toward a healthy skin microbiome not only in patients with a good clinical response but also in patients with a poor clinical response, although the most significant improvements in microbiome diversity were observed in patients with the most robust clinical response. This suggests that the positive effects of dupilumab on the skin microbiome are at least in part independent of clinical improvement.¹

Comments and Clinical Implications

This study by Hartmann et al. further demonstrates the efficacy of treatment with monoclonal antibodies like dupilumab in restoring skin microbiome diversity in patients with AD. However, it is important to note that the study by Hartmann et al. is limited by its relatively small sample size, as well as its non-controlled and non-randomized design. Furthermore, the authors acknowledge that the utilization of DNA from skin surface microbial swabs in their analysis limited their ability to differentiate metabolically active/surviving bacteria from metabolically inactive/dead bacteria. Further research should aim to further elucidate the details of the mechanisms by which treatments like dupilumab restore the skin microbiome. Interestingly, a recent 2024 study by Beck et al. also found treatment with anti-IL13 antibody tralokinumab to positively impact the skin microbiome in AD patients.⁴ These findings by Hartmann et al. and Beck et al. suggest that targeted blockade may have positive impacts on microbial diversity in AD. As we gain a better understanding of how monoclonal antibody treatments affect host antimicrobial response and skin microbial diversity, more targeted therapies for AD and other skin diseases associated with skin microbiome dysfunction may be developed. 

Aileen Park is a medical student at the University of Colorado School of Medicine. Leo Wan is a medical student at the West Virginia School of Osteopathic Medicine. Peter Lio, MD, is a clinical assistant professor of dermatology and pediatrics at Northwestern University School of Medicine and a partner at Medical Dermatology Associates of Chicago. 

1. Hartmann J, Moitinho-Silva L, Sander N, et al. Dupilumab but not cyclosporine treatment shifts the microbiome toward a healthy skin flora in patients with moderate-to-severe atopic dermatitis. Allergy. 2023;78(8):2290-2300. doi:10.1111/all.15742

2. Edslev SM, Agner T, Andersen PS. Skin Microbiome in Atopic Dermatitis. Acta Derm Venereol. 2020;100(12):adv00164. doi:10.2340/00015555-3514

3. Callewaert C, Nakatsuji T, Knight R, et al. IL-4Rα Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis. J Invest Dermatol. 2020;140(1):191. doi:10.1016/j.jid.2019.05.024

4. Beck L, Weidinger S, Tauber M, et al. Neutralizing Interleukin-13 with Tralokinumab Reduces Abundance of S. aureus in Adolescents with Atopic Dermatitis. SKIN J Cutan Med. 2024;8(1):s324-s324. doi:10.25251/skin.8.supp.324