托珠单抗治疗激素抵抗或不耐受的中重度甲状腺相关性眼病临床疗效的Meta分析

Meta-analysis of clinica I efficacy of tocilizumab in the treatment of moderate-to-severe thvroid-associated ophthalmopathy with steroid resistance or intolerance

摘要

目的 探究托珠单抗(tocilizumab, TCZ)治疗激素抵抗或不耐受的中重度甲状腺相关性眼病(thyroid associated ophthalmopathy, TAO)的临床疗效。方法 通过检索中英文数据库(中国知网、中国生物医学、万方、维普、PubMed、Web-of-science、Embase和Cochrane)，检索范围从建库~2024年4月11日发表的关于托珠单抗治疗激素抵抗或不耐受的中重度甲状腺相关眼病的临床研究。评价指标包括临床活动性评分(clinical activity score, CAS)、突眼度、甲状腺刺激免疫球蛋白(thyroid stimulating immunoglobulin, TSI)或促甲状腺激素受体抗体(thyrotropin receptor antibody, TRAb)和不良反应。对纳入的随机对照研究(randomized controlled trial, RCT)使用Jadad评分量表进行质量评价，对纳入的非随机对照试验使用Minors量表进行质量评价。数据提取后使用stata 18.0软件进行Meta分析，连续型变量合并的效应量使用标准化均数差(standard mean difference, SMD)及其95%可信区间(credibility interval, CI)表示。计数资料使用率及95%CI表示。结果 纳入1篇RCT，1篇回顾性队列研究，8篇自身前后对照试验，共计194例研究对象。Meta分析结果显示：托珠单抗治疗激素抵抗或不耐受的中重度TAO可以显著减低CAS评分[SMD=-4.99，95%CI(-6.30~-3.67)，P<0.05]，减少眼球突出度[SMD：-0.81，95%CI(-1.35，-0.27)，P<0.05]，降低TSI/TRAb[SMD=-0.86，95%CI(-1.17~-0.55)，P<0.05]，不良反应事件发生率为[Rate：0.35，95%CI(0.20，0.51)，P<0.05]，轻中度占大多数，严重不良反应事件发生少见。结论 托珠单抗对激素抵抗或不耐受的中重度甲状腺相关性眼病有较好的治疗效果，并且耐受性较好。

Abstract

Objective To investigate the clinical efficacy of tocilizumab (TCZ) in the treatment of moderate-to-severe thyroid-associated ophthalmopathy (TAO) with steroid resistance or intolerance. Methods Relevant clinical studies on tocilizumab for moderate-to-severe TAO with steroid resistance or intolerance were retrieved from the following Chinese and English databases: CNKI, CBM, Wanfang Data, VIP, PubMed, Web of Science, Embase, and Cochrane Library. The retrieval period was from the establishment of each database to April 11, 2024. Evaluation indicators included clinical activity score (CAS), exophthalmos, thyroid-stimulating immunoglobulin (TSI) or thyroid-stimulating hormone receptor antibody (TRAb), and adverse reactions. The quality of included randomized controlled trials (RCTs) was assessed using the Jadad scale, while the quality of non-randomized controlled trials was evaluated with the Minors scale. After data extraction, meta-analysis was performed using Stata 18.0 software. For continuous variables, the combined effect size was expressed as standardized mean difference (SMD) with 95% confidence interval (CI). For count data, the rate with 95% CI was used. Results A total of 1 RCT, 1 retrospective cohort study, and 8 before-after self-controlled trials were included, involving 194 subjects. The meta-analysis results showed that tocilizumab significantly reduced CAS [SMD=-4.99, 95%CI (-6.30, -3.67), P<0.05], decreased exophthalmos [SMD=-0.81, 95%CI (-1.35, -0.27), P<0.05], and lowered TSI/TRAb [SMD=-0.86, 95%CI (-1.17, -0.55), P<0.05]. and lowered TSI/TRAb [SMD=-0.86, 95%CI(-1.17, -0.55), P<0.05]. The incidence of adverse reactions was 0.35 [95%CI(0.20, 0.51), P<0.05], with most being mild to moderate and severe adverse reactions being rare. Conclusion Tocilizumab has a good therapeutic effect and favorable tolerance in the treatment of moderate-to-severe TAO with steroid resistance or intolerance.

关键词

托珠单抗 / 甲状腺相关性眼病 / Graves眼病 / 治疗效果 / Meta分析

Key words

Tocilizumab / Thyroid associated ophthalmopathy / Graves Ophthalmopathy / Therapeutic effect / Meta-analysis

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基金资助

湖南省教育厅优秀青年项目(22B0066)

长沙市自然科学基金(kq2208114)