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总嗜酸性粒细胞计数作为乌帕替尼治疗特应性皮炎 48 周疗效的生物标志物。

Total eosinophil count as a biomarker for therapeutic effects of upadacitinib in atopic dermatitis over 48 weeks.

机构信息

Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan.

Department of Dermatology, Nippon Medical School, Tokyo, Japan.

出版信息

Front Immunol. 2024 Apr 30;15:1365544. doi: 10.3389/fimmu.2024.1365544. eCollection 2024.

Abstract

BACKGROUND

Atopic dermatitis (AD) is a chronic skin disease characterized by type 2-skewed immune responses, and significantly influenced by cytokines dependent on Janus kinases (JAKs). Upadacitinib, a JAK1 inhibitor, is effective for moderate-to-severe AD. This study aims to identify biomarkers that reflect long-term therapeutic effects of upadacitinib 15 mg or 30 mg.

METHODS

A retrospective study from August 2021 to July 2023 included 213 AD patients treated with upadacitinib 15 mg and 70 AD patients with 30 mg. We analyzed eczema area and severity index (EASI), peak pruritus-numerical rating scale (PP-NRS), serum immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), and total eosinophil count (TEC) at weeks 0, 4, 12, 24, 36, and 48 of treatment.

RESULTS

Both treatments with upadacitinib 15 mg and 30 mg significantly reduced EASI and PP-NRS scores over week 4 to 48 compared to baseline. Upadacitinib 15 mg or 30 mg treatment significantly decreased TEC compared to baseline through week 4 to 36 or week 4 to 48, respectively. The percent reduction of TEC correlated with those of EASI and PP-NRS through week 4 to 48 of treatment with upadacitinib 15 mg, or through week 12 to 48 with 30 mg, respectively. After adjusting for % reductions of other laboratory markers, the significance of correlations was preserved at weeks 36 and 48 of 15 mg treatment, while at weeks 4 and 36 of 30 mg treatment.

CONCLUSION

The % reduction of TEC correlated with those of EASI and PP-NRS during upadacitinib treatment, indicating its potential as a biomarker reflecting treatment responses to upadacitinib in AD patients. However, the variability of significant correlation during treatment indicates that further inspection is needed for its usefulness in monitoring responses to upadacitinib treatment for AD.

摘要

背景

特应性皮炎(AD)是一种慢性皮肤病,其特征为 2 型免疫反应偏倚,并受依赖于 Janus 激酶(JAK)的细胞因子显著影响。JAK1 抑制剂乌帕替尼在中重度 AD 中有效。本研究旨在确定反映乌帕替尼 15mg 或 30mg 长期治疗效果的生物标志物。

方法

一项回顾性研究纳入了 213 例接受乌帕替尼 15mg 治疗的 AD 患者和 70 例接受乌帕替尼 30mg 治疗的 AD 患者,该研究于 2021 年 8 月至 2023 年 7 月进行。我们分析了治疗第 0、4、12、24、36 和 48 周时的湿疹面积和严重程度指数(EASI)、瘙痒峰值数字评分量表(PP-NRS)、血清免疫球蛋白 E(IgE)、胸腺激活调节趋化因子(TARC)、乳酸脱氢酶(LDH)和总嗜酸性粒细胞计数(TEC)。

结果

与基线相比,乌帕替尼 15mg 和 30mg 治疗均显著降低了 EASI 和 PP-NRS 评分,从第 4 周到第 48 周。与基线相比,乌帕替尼 15mg 或 30mg 治疗分别在第 4 周到第 36 周或第 4 周到第 48 周显著降低了 TEC。与乌帕替尼 15mg 治疗的第 4 周到第 48 周或与 30mg 治疗的第 12 周到第 48 周的 EASI 和 PP-NRS 相比,TEC 的百分比降低与治疗期间的 EASI 和 PP-NRS 相关。在调整其他实验室标志物的百分比降低后,乌帕替尼 15mg 治疗的第 36 周和第 48 周以及乌帕替尼 30mg 治疗的第 4 周和第 36 周的相关性仍具有统计学意义。

结论

在乌帕替尼治疗期间,TEC 的百分比降低与 EASI 和 PP-NRS 相关,表明其作为 AD 患者对乌帕替尼治疗反应的生物标志物具有潜力。然而,在治疗期间,显著相关性的变异性表明,需要进一步检查其在监测 AD 患者对乌帕替尼治疗反应方面的有用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cdb/11091278/fb620d2c41cf/fimmu-15-1365544-g001.jpg

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