Dataset Information

Changes in Skin and Nasal Microbiome and Staphylococcal Species Following Treatment of Atopic Dermatitis with Dupilumab.

ABSTRACT: Investigation of changes in the skin microbiome following treatment of atopic dermatitis (AD) with dupilumab may provide valuable insights into the skin microbiome as a therapeutic target. The aim of this study is to assess changes in the AD skin microbiome following treatment of AD with dupilumab (n = 27). E-swabs were collected from nose, lesional, and nonlesional skin before and after 16 weeks of dupilumab therapy, and the microbiome was analyzed by 16S rRNA and tuf gene sequencing. Data for 17 patients with milder disease receiving treatment with non-targeted therapies are also presented. The results show that both groups experienced clinical improvement (p < 0.001) following dupilumab therapy and that Shannon diversity increased and bacterial community structure changed. The relative abundance of the genus Staphylococcus (S.) and S. aureus decreased, while that of S. epidermidis and S. hominis increased. No significant changes were observed for patients receiving non-targeted treatments. The increases in S. epidermidis and S. hominis and the decrease in S. aureus correlated with clinical improvement. Furthermore, changes in S. hominis and S. epidermidis correlated inversely with S. aureus. In conclusion, treatment with dupilumab significantly changed the skin microbiome and decreased S. aureus. Our results suggest a favorable role of commensal staphylococci in AD.

SUBMITTER: Olesen CM

PROVIDER: S-EPMC8303790 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Changes in Skin and Nasal Microbiome and Staphylococcal Species Following Treatment of Atopic Dermatitis with Dupilumab.

Olesen Caroline Meyer CM Ingham Anna Cäcilia AC Thomsen Simon Francis SF Clausen Maja-Lisa ML Andersen Paal Skytt PS Edslev Sofie Marie SM Yüksel Yasemin Topal YT Guttman-Yassky Emma E Agner Tove T

Microorganisms 20210713 7

Investigation of changes in the skin microbiome following treatment of atopic dermatitis (AD) with dupilumab may provide valuable insights into the skin microbiome as a therapeutic target. The aim of this study is to assess changes in the AD skin microbiome following treatment of AD with dupilumab (<i>n</i> = 27). E-swabs were collected from nose, lesional, and nonlesional skin before and after 16 weeks of dupilumab therapy, and the microbiome was analyzed by 16S rRNA and <i>tuf</i> gene sequenc ...[more]

PMID: 34361924

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Project description:IntroductionAtopic dermatitis (AD), with its hallmark symptoms of pruritus and skin lesions, often impairs patients' quality of life. We assessed time spent with clear/almost clear skin and no/minimal itch during upadacitinib treatment versus placebo or dupilumab among patients with moderate-to-severe AD.MethodsThis analysis consisted of a post hoc analysis of Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 were replicate, randomized, double-blind, placebo-controlled phase 3 studies with patients randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 16 weeks. Heads Up was a head-to-head, randomized, double-blind, double-dummy, phase 3b study with patients randomized (1:1) to upadacitinib 30 mg or subcutaneous dupilumab 300 mg for 24 weeks. Skin clearance was assessed with the Eczema Area and Severity Index (EASI) at baseline, weeks 1, 2, and 4, and every 4 weeks thereafter. Itch was assessed using the Worst Pruritus Numerical Rating Scale (WP-NRS) daily over 16 weeks and every 2 weeks thereafter to week 24 in Heads Up.ResultsThis analysis included 1683 patients in Measure Up 1 and 2 and 673 patients in Heads Up. Through 16 weeks in Measure Up 1 and 2, patients receiving upadacitinib spent 9.8-13.4 times as many days with an EASI 90 response and 7.0-10.3 times as many days with a WP-NRS 0/1 response versus placebo. In Heads Up, patients receiving upadacitinib spent 2.0 and 1.7 times as many days through 16 and 24 weeks, respectively, with an EASI 90 response versus dupilumab. Through 16 and 24 weeks, patients receiving upadacitinib spent 3.0 and 2.6 times as many days, respectively, with a WP-NRS 0/1 response versus dupilumab.ConclusionsPatients with moderate-to-severe AD spent more time with clear/almost clear skin and no/minimal itch with upadacitinib versus placebo or dupilumab.Trial registrationClinicalTrials.gov identifier, Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), Heads Up (NCT03738397).

Project description:ObjectiveTo elucidate the pathogenesis of dupilumab (Dupixent®)-associated ocular surface disease (DAOSD).DesignProspective single-center cohort study.SubjectsTwenty patients with moderate-to-severe atopic dermatitis (AD) who received dupilumab and 10 age- and sex-matched healthy controls were enrolled in the study.MethodsThe study cohort underwent a thorough slit-lamp and entire-body dermatologic examination. Conjunctival swabs and smears were collected at baseline, 4 and 16 weeks after treatment initiation, and during the conjunctivitis episode. To analyse the ocular surface microbiome, 16S ribosomal RNA sequencing was performed, smears were hematoxylin and eosin stained, and serum cytokines were measured by using a multiplex immunobead assay.Main outcome measuresComposition of ocular surface microbiome and cellular component as well as serum cytokine levels.ResultsSix of the 20 patients with AD developed DAOSD after dupilumab initiation; these patients responded after a delay to treatment as quantified by Eczema Area and Severity Index and Investigator's Global Assessment score. Conjunctival smears showed massive neutrophilic infiltration and serum analysis revealed increased systemic levels of neutrophil-priming proinflammatory cytokines, in particular interleukin-1β and tumor necrosis factor α, in patients with DAOSD compared with those without it. The ocular surface microbiome of patients with DAOSD was characterized by a diverse and persistent microbial colonization, particularly by Acetobacter aceti. In contrast, microbial diversity decreased in patients with AD without DAOSD after the initiation of dupilumab treatment, especially the abundance of Staphylococcus aureus. In vitro experiments substantiated the potential role of the microbiome, showing increased growth of A. aceti and decreased growth of S. aureus in presence of dupilumab.ConclusionsPersistent neutrophilic infiltration and a unique microbial landscape on the ocular surface associated with elevated levels of systemic proinflammatory cytokines typify DAOSD.Financial disclosuresProprietary or commercial disclosure may be found after the references.

Dataset Information

Changes in Skin and Nasal Microbiome and Staphylococcal Species Following Treatment of Atopic Dermatitis with Dupilumab.

Publications

Changes in Skin and Nasal Microbiome and Staphylococcal Species Following Treatment of Atopic Dermatitis with Dupilumab.

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