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Janus 激酶抑制剂治疗特应性皮炎的疗效和安全性:系统评价和荟萃分析。

Efficacy and Safety of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis: A Systematic Review and Meta-Analysis.

机构信息

Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China.

Department of Immunology, China Medical University, Shenyang, China.

出版信息

Dermatology. 2022;238(4):725-735. doi: 10.1159/000518541. Epub 2021 Aug 27.

Abstract

BACKGROUND

Current therapeutic options for atopic dermatitis (AD) are limited. Janus kinase (JAK) inhibitors may be viable alternatives.

OBJECTIVES

To assess the efficacy and safety of JAK inhibitors for AD treatment.

METHODS

We searched PubMed, Embase, the Cochrane Controlled Register of Trials, Web of Science, Global Resource of Eczema Trials database, and ClinicalTrials.gov from inception to September 1, 2020. Randomized clinical trials (RCTs) comparing JAK inhibitors with placebo/vehicle treatment for AD patients were included. The primary study outcomes included (1) the change (%) from the Eczema Area and Severity Index (EASI) baseline expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI), and (2) the Investigator's Global Assessment (IGA) response and safety outcomes expressed as relative risk (RR) and 95% CI.

RESULTS

We included 14 RCTs published in 13 studies (3,822 patients). Treatment with JAK inhibitors significantly improved IGA response (RR 2.83, 95% CI 2.25-3.56, p < 0.001) and EASI score (WMD -28.82, 95% CI -34.48 to -23.16, p < 0.001). JAK inhibitor treatment achieved the largest improvement in both IGA response (RR 3.59, 95% CI 2.66-4.84, p < 0.001) and EASI score (WMD -42.00, 95% CI -48.64 to -35.36, p < 0.001) by week 4 of treatment. Topical JAK inhibitors were significantly more efficacious than oral inhibitors. Upadacitinib treatment for 4 weeks was most effective in reducing EASI score (WMD -53.92, 95% CI -69.26 to -38.58, p < 0.001), while abrocitinib for 4 weeks led to the most effective IGA response (RR 5.47, 95% CI 2.74-10.93, p < 0.001). There was no difference in the frequency of adverse events (AEs) leading to discontinuation; however, JAK inhibitors use, especially abrocitinib, led to a higher incidence of treatment-emergent AEs (RR 1.25, 95% CI 1.10-1.42, p = 0.001).

CONCLUSION

Our results imply that JAK inhibitors are an effective and safe AD treatment. Nevertheless, further trials with longer duration and head-to-head comparisons of different JAK inhibitors are needed.

摘要

背景

目前治疗特应性皮炎(AD)的方法有限。Janus 激酶(JAK)抑制剂可能是可行的替代方法。

目的

评估 JAK 抑制剂治疗 AD 的疗效和安全性。

方法

我们从建库至 2020 年 9 月 1 日在 PubMed、Embase、Cochrane 对照试验注册库、Web of Science、全球湿疹试验数据库和 ClinicalTrials.gov 中检索了比较 JAK 抑制剂与 AD 患者安慰剂/载体治疗的随机临床试验(RCT)。主要研究结局包括(1)用加权均数差值(WMD)和 95%置信区间(95%CI)表示的 Eczema Area and Severity Index(EASI)基线的变化(%),以及(2)用相对风险(RR)和 95%CI 表示的研究者全球评估(IGA)反应和安全性结局。

结果

我们纳入了 13 项研究中的 14 项 RCT 发表的研究(3822 例患者)。JAK 抑制剂治疗显著改善了 IGA 反应(RR 2.83,95%CI 2.25-3.56,p<0.001)和 EASI 评分(WMD -28.82,95%CI -34.48 至 -23.16,p<0.001)。JAK 抑制剂治疗在第 4 周时在 IGA 反应(RR 3.59,95%CI 2.66-4.84,p<0.001)和 EASI 评分(WMD -42.00,95%CI -48.64 至 -35.36,p<0.001)方面取得了最大的改善。局部 JAK 抑制剂比口服抑制剂更有效。乌帕替尼治疗 4 周可显著降低 EASI 评分(WMD -53.92,95%CI -69.26 至 -38.58,p<0.001),而阿布昔替尼治疗 4 周可导致 IGA 反应最有效(RR 5.47,95%CI 2.74-10.93,p<0.001)。导致停药的不良事件(AE)发生率无差异;然而,JAK 抑制剂的使用,尤其是阿布昔替尼,导致治疗出现的 AE 发生率更高(RR 1.25,95%CI 1.10-1.42,p=0.001)。

结论

我们的结果表明 JAK 抑制剂是一种有效且安全的 AD 治疗方法。然而,仍需要进行持续时间更长的试验以及不同 JAK 抑制剂的头对头比较。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d849/9393843/2eed70ab273b/drm-0238-0725-g01.jpg

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