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Janus 激酶抑制剂治疗斑秃:系统评价和荟萃分析。

Janus Kinase Inhibitors for Alopecia Areata: A Systematic Review and Meta-Analysis.

机构信息

Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

出版信息

JAMA Netw Open. 2023 Jun 1;6(6):e2320351. doi: 10.1001/jamanetworkopen.2023.20351.

Abstract

IMPORTANCE

Alopecia areata (AA) is a common chronic tissue-specific autoimmune disease. Several studies have reported outcomes of Janus kinase (JAK) inhibitors for treating AA, but limited evidence has emerged.

OBJECTIVE

To evaluate the effectiveness and safety associated with JAK inhibitors for AA.

DATA SOURCES

MEDLINE, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) were searched from inception until August 2022.

STUDY SELECTION

Only randomized clinical trials (RCTs) were included. Pairs of reviewers independently and in duplicate selected the studies.

DATA EXTRACTION AND SYNTHESIS

Hartung-Knapp-Sidik-Jonkman random-effects models were used for meta-analysis. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.

MAIN OUTCOMES AND MEASURES

The primary outcomes of interest were (1) proportion of patients who achieved 30%, 50%, and 90% improvement in Severity of Alopecia Tool (SALT) score from baseline, (2) change from baseline SALT score, and (3) treatment-related adverse event (AE).

RESULTS

Seven RCTs with 1710 patients (1083 females [63.3%]; mean [SD] age range, 36.3 [10.4] to 69.7 [16.2] years) were eligible and included in the study. JAK inhibitors were associated with more patients achieving 50% improvement (odds ratio [OR], 5.28 [95% CI, 1.69-16.46]; GRADE assessment: low certainty) and 90% improvement (OR, 8.15 [95% CI, 4.42-15.03]; GRADE assessment: low certainty) in SALT score from baseline compared with placebo. JAK inhibitors were associated with more lowered SALT scores from the baseline compared with placebo (mean difference [MD], -34.52 [95% CI, -37.80 to -31.24]; GRADE assessment: moderate certainty), and JAK inhibitors were not associated with more treatment-related AEs (relative risk [RR], 1.25 [95% CI, 1.00-1.57]; GRADE assessment: high certainty) compared with placebo. High certainty of evidence showed that JAK inhibitors may not be associated with more severe AEs compared with placebo (RR, 0.77; 95% CI, 0.41-1.43). The subgroup analysis showed that oral JAK inhibitors were more efficient than placebo (change from baseline SALT scores: MD, -36.80; 95% CI, -39.57 to -34.02), and no difference was found between external JAK inhibitors and placebo (change from baseline SALT scores: MD, -0.40; 95% CI, -11.30 to 10.50).

CONCLUSIONS AND RELEVANCE

Results of this systematic review and meta-analysis suggest that JAK inhibitors, compared with placebo, were associated with hair regrowth and that the outcome of oral JAK inhibitors was better than the external route of administration. Although the safety and tolerability of JAK inhibitors were acceptable, longer RCTs are needed to further assess the effectiveness and safety of these treatments for AA.

摘要

重要性

斑秃(AA)是一种常见的慢性组织特异性自身免疫性疾病。几项研究报告了 Janus 激酶(JAK)抑制剂治疗 AA 的结果,但有限的证据已经出现。

目的

评估 JAK 抑制剂治疗 AA 的有效性和安全性。

数据来源

从成立到 2022 年 8 月,MEDLINE、Embase 和 Cochrane 中央对照试验注册中心(Cochrane Central Register of Controlled Trials)进行了搜索。

研究选择

仅包括随机临床试验(RCT)。 pairs of reviewers independently and in duplicate selected the studies.

数据提取和综合

采用 Hartung-Knapp-Sidik-Jonkman 随机效应模型进行荟萃分析。使用推荐分级评估、制定与评价(GRADE)方法评估证据的确定性。本研究按照系统评价和荟萃分析的首选报告项目(PRISMA)报告指南进行报告。

主要结果和措施

主要观察指标是(1)从基线开始,患者达到严重程度脱发评分(SALT)评分改善 30%、50%和 90%的比例,(2)从基线开始 SALT 评分的变化,和(3)与治疗相关的不良事件(AE)。

结果

7 项 RCT 共纳入 1710 例患者(1083 例女性[63.3%];平均[标准差]年龄范围为 36.3[10.4]至 69.7[16.2]岁)符合纳入标准并纳入研究。与安慰剂相比,JAK 抑制剂更能使更多的患者达到 SALT 评分 50%(优势比[OR],5.28 [95%置信区间[CI],1.69-16.46];GRADE 评估:低确定性)和 90%(OR,8.15 [95% CI,4.42-15.03];GRADE 评估:低确定性)的改善。与安慰剂相比,JAK 抑制剂更能降低 SALT 评分(平均差异[MD],-34.52 [95% CI,-37.80 至-31.24];GRADE 评估:中等确定性),与安慰剂相比,JAK 抑制剂与更多的治疗相关 AEs 无关(相对风险[RR],1.25 [95% CI,1.00-1.57];GRADE 评估:高确定性)。高确定性证据表明,与安慰剂相比,JAK 抑制剂可能不会引起更严重的 AE(RR,0.77;95% CI,0.41-1.43)。亚组分析显示,口服 JAK 抑制剂比安慰剂更有效(从基线开始 SALT 评分的变化:MD,-36.80;95% CI,-39.57 至-34.02),而外用 JAK 抑制剂与安慰剂之间没有差异(从基线开始 SALT 评分的变化:MD,-0.40;95% CI,-11.30 至 10.50)。

结论和相关性

本系统评价和荟萃分析的结果表明,与安慰剂相比,JAK 抑制剂与毛发生长有关,口服 JAK 抑制剂的效果优于外用途径。尽管 JAK 抑制剂的安全性和耐受性可以接受,但需要更长时间的 RCT 来进一步评估这些治疗方法治疗 AA 的有效性和安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1743/10300710/61899ae6212f/jamanetwopen-e2320351-g001.jpg

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