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托珠单抗治疗 Takayasu 动脉炎的疗效及其与肿瘤坏死因子 α 抑制剂的比较:系统评价和荟萃分析。

The effectiveness of tocilizumab and its comparison with tumor necrosis factor alpha inhibitors for Takayasu Arteritis: A systematic review and meta-analysis.

机构信息

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.

School of Telemedicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow 226014, India.

出版信息

Autoimmun Rev. 2023 Mar;22(3):103275. doi: 10.1016/j.autrev.2023.103275. Epub 2023 Jan 15.

Abstract

Takayasu arteritis (TAK) refractory to conventional disease-modifying anti-rheumatic drugs (DMARDs) is commonly treated with biologic DMARDs such as tocilizumab or tumor necrosis factor-alpha inhibitors (TNFi). The 2021 American College of Rheumatology (ACR) recommendations preferred TNFi to tocilizumab. Therefore, we conducted a systematic review with meta-analysis to assess the evidence base for tocilizumab in TAK by updating a previous systematic review on DMARDs in TAK through searches on MEDLINE, Pubmed Central, Scopus, major international Rheumatology conference abstracts, and clinical trial databases from January 2021 to November 2022. Thirty-five studies involving 1082 TAK [one randomized controlled trial (RCT), eleven controlled and twenty-one uncontrolled studies, most of moderate to high quality] had evaluated tocilizumab in TAK. The RCT of tocilizumab versus placebo failed to meet its primary end-point of superiority of tocilizumab on an intention-to-treat analysis (hazard ratio 0.41, 95%CI 0.15-1.10) but successfully met the secondary end-point of superiority on per-protocol analysis (hazard ratio 0.34, 95%CI 0.11-1.00). A meta-analysis of six studies identified similar rates of clinical remission [risk ratio (RR) tocilizumab vs TNFi 1.03, 95%CI 0.91-1.17)], angiographic stabilization (RR 1.00, 95%CI 0.72-1.40) or adverse events (RR 0.84, 95%CI 0.54-1.31) with tocilizumab or TNFi. A meta-analysis of three studies identified superior clinical response (RR 1.55, 95%CI 1.15-2.10) and adverse effect profile (RR 0.45, 95%CI 0.25-0.80) with tocilizumab than cyclophosphamide. Pooled data from uncontrolled studies identified clinical response in 85%(95%CI 79-91%) and angiographic stabilization in 82% (95%CI 68-94%). Our study suggests similar evidence for treating TAK with tocilizumab or TNFi, contrary to the ACR 2021 recommendations.

摘要

大动脉炎(TAK)对传统的疾病修饰抗风湿药物(DMARDs)治疗无效,通常使用生物 DMARDs 治疗,如托珠单抗或肿瘤坏死因子-α抑制剂(TNFi)。2021 年美国风湿病学会(ACR)的建议优先选择 TNFi 而不是托珠单抗。因此,我们通过在 2021 年 1 月至 2022 年 11 月期间在 MEDLINE、PubMed Central、Scopus、主要国际风湿病会议摘要和临床试验数据库中进行搜索,对托珠单抗治疗 TAK 的证据进行了系统回顾和荟萃分析,更新了之前关于 TAK 中 DMARDs 的系统综述。35 项研究共纳入 1082 例 TAK[1 项随机对照试验(RCT)、11 项对照研究和 21 项非对照研究,大多数为中高质量]评估了托珠单抗在 TAK 中的作用。托珠单抗与安慰剂的 RCT 未能达到其主要终点,即托珠单抗在意向治疗分析中的优越性(危险比 0.41,95%CI 0.15-1.10),但成功达到了次要终点,即方案分析中的优越性(危险比 0.34,95%CI 0.11-1.00)。六项研究的荟萃分析确定了托珠单抗与 TNFi 之间相似的临床缓解率[风险比(RR)托珠单抗与 TNFi 1.03,95%CI 0.91-1.17]、血管造影稳定率(RR 1.00,95%CI 0.72-1.40)或不良事件发生率(RR 0.84,95%CI 0.54-1.31)。三项研究的荟萃分析确定了托珠单抗优于环磷酰胺的临床反应(RR 1.55,95%CI 1.15-2.10)和不良影响谱(RR 0.45,95%CI 0.25-0.80)。来自非对照研究的汇总数据确定了 85%(95%CI 79-91%)的临床反应和 82%(95%CI 68-94%)的血管造影稳定率。我们的研究表明,托珠单抗或 TNFi 治疗 TAK 的证据相似,与 ACR 2021 年的建议相反。

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