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曲罗芦单抗治疗可通过增加中度至重度特应性皮炎成人患者的微生物多样性来改善皮肤微生物群:一项随机对照试验(ECZTRA 1)中的微生物多样性分析。

Tralokinumab treatment improves the skin microbiota by increasing the microbial diversity in adults with moderate-to-severe atopic dermatitis: Analysis of microbial diversity in ECZTRA 1, a randomized controlled trial.

作者信息

Beck Lisa A, Bieber Thomas, Weidinger Stephan, Tauber Marie, Saeki Hidehisa, Irvine Alan D, Eichenfield Lawrence F, Werfel Thomas, Arlert Petra, Jiang Li, Røpke Mads, Paller Amy S

机构信息

Department of Dermatology, Medicine and Pathology, University of Rochester Medical Center, Rochester, New York.

Department of Dermatology and Allergy, University Hospital, Bonn, Germany; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland.

出版信息

J Am Acad Dermatol. 2023 Apr;88(4):816-823. doi: 10.1016/j.jaad.2022.11.047. Epub 2022 Dec 5.

Abstract

BACKGROUND

Atopic dermatitis (AD) is characterized by microbial dysbiosis, immune dysregulation, and an impaired skin barrier. Microbial dysbiosis in AD involves a reduction in diversity primarily driven by an increased abundance of Staphylococcus aureus. Tralokinumab, an approved treatment for adults with moderate-to-severe AD, improves the skin barrier and immune abnormalities by specifically targeting the interleukin 13 cytokine, but its impact on the skin microbiome is unknown.

OBJECTIVE

To investigate how tralokinumab affects the skin microbiome by examining the lesional skin of adults with moderate-to-severe AD from the phase 3 ECZTRA 1 trial (NCT03131648).

METHODS

Microbiome profiling, S aureus abundance, and biomarker data were assessed in a subset of ECZTRA 1 participants (S aureus abundance at baseline and week 16; microbiome profiling at baseline, and week 8/16; and serum sampling before dose and week 4/8/16/28/52).

RESULTS

Tralokinumab treatment led to increased microbial diversity, reduced S aureus abundance, and increased abundance of the commensal coagulase-negative Staphylococci.

LIMITATIONS

Limitations include a lack of S aureus abundance data at week 8, sampling site variation between participants, and possible influence from concomitant systemic antiinfectives.

CONCLUSION

Our findings indicate specific targeting of the interleukin 13 cytokine with tralokinumab can directly and/or indirectly improve microbial dysbiosis seen in AD skin.

摘要

背景

特应性皮炎(AD)的特征是微生物群落失调、免疫调节异常和皮肤屏障受损。AD中的微生物群落失调主要表现为多样性降低,这主要是由金黄色葡萄球菌丰度增加所驱动。曲罗芦单抗是一种已获批用于治疗中度至重度AD成人患者的药物,它通过特异性靶向白细胞介素13细胞因子来改善皮肤屏障和免疫异常,但其对皮肤微生物群的影响尚不清楚。

目的

通过研究3期ECZTRA 1试验(NCT03131648)中中度至重度AD成人患者的皮损,探讨曲罗芦单抗如何影响皮肤微生物群。

方法

对ECZTRA 1试验的一部分参与者进行微生物群分析、金黄色葡萄球菌丰度和生物标志物数据评估(基线和第16周时的金黄色葡萄球菌丰度;基线、第8周/16周时的微生物群分析;给药前以及第4/8/16/28/52周时的血清采样)。

结果

曲罗芦单抗治疗导致微生物多样性增加、金黄色葡萄球菌丰度降低以及共生凝固酶阴性葡萄球菌丰度增加。

局限性

局限性包括第8周时缺乏金黄色葡萄球菌丰度数据、参与者之间的采样部位差异以及全身性抗感染药物的潜在影响。

结论

我们的研究结果表明,用曲罗芦单抗特异性靶向白细胞介素13细胞因子可直接和/或间接改善AD皮肤中出现的微生物群落失调。

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