Dupilumab but not cyclosporine treatment shifts the microbiome toward a healthy skin flora in patients with moderate‐to‐severe atopic dermatitis

Hartmann, Jan; Moitinho‐Silva, Lucas; Sander, Nicole; Harder, Inken; Häsler, Robert; Rodríguez, Elke; Haufe, Eva; Kleinheinz, Andreas; Abraham, Susanne; Heratizadeh, Annice; Weißhaar, Elke; Schäkel, Knut; Handrick, Christiane; Augustin, Matthias; Wollenberg, Andreas; Staubach‐Renz, Petra; Ertner, Konstantin; Sticherling, Michael; Schwarz, Beate; Quist, Sven; Wiemers, Franca; Schenck, Florian; Wildberger, Julia; Tittmann, Lukas; Lieb, Wolfgang; Schmitt, Jochen; Werfel, Thomas; Weidinger, Stephan

doi:10.1111/all.15742

Cited by 12 publications

(5 citation statements)

References 48 publications

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“…A similar association was reported for BMI and AD, formulating the hypothesis that hypertrophied adipocytes contribute to a pro-inflammatory state [44]. Anti-inflammatory drugs such as dupilumab ameliorate immune system regulation and the skin microbiome, but they probably have fewer effects on the above-mentioned factors that link depressive disorders and obesity [45]. This consideration is supported by the observation in our study of the persistence of depressive symptoms in patients whose dermatological disease has a lesser impact on their quality of life; this aspect can seem paradoxical, but it identifies subjects that suffer from mood disorders independently from the distress associated with AD [46].…”

Section: Discussionsupporting

confidence: 60%

Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

Ferrucci,

Tavecchio,

Ceresa

et al. 2024

JCM

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Background: Atopic Dermatitis (AD) is a prevalent inflammatory skin disease whose course is often complicated by the presence of concomitant anxiety and depressive disorders. Dupilumab has been demonstrated to be largely effective in AD. The aims of the present study were to (1) to verify the effectiveness of 2-year dupilumab treatment on the depressive and anxiety symptoms of patients affected by AD and (2) to identify predictors of the persistence of psychiatric symptoms despite maintenance treatment with dupilumab. Methods: A total of 331 patients with severe AD were assessed at baseline and at different times over 2 years by a large set of rating scales, including the Eczema Area and Severity Index (EASI), the Hospital Anxiety and Depression Scale (HADS), and the Dermatology Life Quality Index (DLQI). Paired sample t-tests were performed to verify the effectiveness of dupilumab on the severity of AD and mental health items. Two binary logistic regression models were then used to identify the predictors of the persistence of clinically significant depression and anxiety, defined by a score ≥ 8 on each sub-scale of the HADS. Results: After 2 years of treatment with dupilumab, the patients benefited, showing a significant improvement in both the dermatological disease and comorbid depression/anxiety (p < 0.001 for all scales). Overall, 17.5% and 13% of patients, respectively, reported residual depressive and anxiety symptoms after the 2-year treatment with dupilumab. The baseline predictors of the persistence of clinically significant depressive symptoms after the 2-year treatment with dupilumab were found to be a higher body mass index (BMI) (p = 0.012), a lower impact of dermatological disease on quality of life (p = 0.015), and more severe depressive symptoms (p < 0.01), while for anxiety, the only predictor was found to be female gender (p = 0.03). Conclusions: Using a multidisciplinary approach, at baseline, dermatologists should more closely monitor patients who are at a greater risk of maintaining residual psychiatric symptoms despite therapy, such as those with more severe depressive symptoms and those who are overweight.

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Section: Discussionsupporting

confidence: 60%

Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

Ferrucci,

Tavecchio,

Ceresa

et al. 2024

JCM

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“…Dupilumab therapy has been demonstrated to increase the diversity of the skin bacterial microbiome while decreasing S aureus colonization as observed in numerous clinical studies [ 12 , 31 , 32 , 33 , 34 ]. Corresponding findings were also obtained in this study.…”

Section: Discussionmentioning

confidence: 99%

Dupilumab Alters Both the Bacterial and Fungal Skin Microbiomes of Patients with Atopic Dermatitis

Umemoto,

Kakurai,

Matsumoto

et al. 2024

Microorganisms

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The skin microbiome at lesion sites in patients with atopic dermatitis (AD) is characterized by dysbiosis. Although the administration of dupilumab, an IL-4Rα inhibitor, improves dysbiosis in the bacterial microbiome, information regarding the fungal microbiome remains limited. This study administered dupilumab to 30 patients with moderate-to-severe AD and analyzed changes in both fungal and bacterial skin microbiomes over a 12-week period. Malassezia restricta and M. globosa dominated the fungal microbiome, whereas non-Malassezia yeast species increased in abundance, leading to greater microbial diversity. A qPCR analysis revealed a decrease in Malassezia colonization following administration, with a higher reduction rate observed where the pretreatment degree of colonization was higher. A correlation was found between the group classified by the Eczema Area and Severity Index, the group categorized by the concentration of Thymus and activation-regulated chemokine, and the degree of skin colonization by Malassezia. Furthermore, an analysis of the bacterial microbiome also confirmed a decrease in the degree of skin colonization by the exacerbating factor Staphylococcus aureus and an increase in the microbial diversity of the bacterial microbiome. Our study is the first to show that dupilumab changes the community structure of the bacterial microbiome and affects the fungal microbiome in patients with AD.

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“…28 In a clinical investigation with microbiologic relevance, Jan Hartmann et al examined skin swabs from 157 patients for 16S rRNA gene amplicon sequencing both before and after they had a three-month course of treatment with dupilumab or cyclosporine. 29 A possible impact of IL-4Rα blocking on the microbiome is suggested by the findings, which show that systemic therapy with dupilumab rather than cyclosporine tends to rebuild a healthy skin microbiome, mainly independent of clinical response. These studies suggest that microbiome and skin barrier function have been beneficially affected by biologics that target IL-4 and IL-13.…”

Section: Mechanisms Of Dupilumabmentioning

confidence: 99%

A Review of Dupilumab in the Treatment of Atopic Dermatitis in Infants and Children

Wang,

Gao,

Zhang

2024

DDDT

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Atopic dermatitis (AD), a common pruritic and chronic inflammatory skin disease, has a major impact on a patient’s quality of life. It is characterized by dry, itchy, and eczema-like rashes. AD is more prevalent in young children and has been linked to a variety of other allergy disorders. Traditional drug therapy has certain limitations for treating young children with AD. However, biologics have good clinical application prospects in the medical treatment of young patients. Dupilumab, a fully human monoclonal antibody, specifically binds to the IL-4 Rα subunit, inhibiting IL-4 and IL-13 signaling and blocking the occurrence of type 2 inflammatory response. It has a good effect on treating infants and children with moderate-to-severe AD. This review explores the safety and efficacy of dupilumab in the treatment of AD in infants and children and the impact of early intervention on AD progression, with the aim of informing clinical practice in the use of dupilumab for the treatment of young patients with AD.

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Dupilumab but not cyclosporine treatment shifts the microbiome toward a healthy skin flora in patients with moderate‐to‐severe atopic dermatitis

Abstract: HARTMANN et al.

Cited by 12 publications

References 48 publications

Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

Dupilumab Alters Both the Bacterial and Fungal Skin Microbiomes of Patients with Atopic Dermatitis

A Review of Dupilumab in the Treatment of Atopic Dermatitis in Infants and Children

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