Yang Wuxia, Wang Aidi, Liu Baoshan
Department of Traditional Chinese Medicine, Tianjin Medical University General Hospital, Tianjin, China.
Front Med (Lausanne). 2025 May 20;12:1580264. doi: 10.3389/fmed.2025.1580264. eCollection 2025.
Remarkable clinical benefits have been achieved for patients with haemophilia through intravenously administered adeno-associated virus (AAV)-based liver-directed gene therapy. However, no comprehensive meta-analysis based on hemophilia types, various transgene types, AAV capsid, neutralizing antibody titers, and baseline factor VIII activity has been conducted to assess the efficacy of AAV vector gene therapy in hemophilic patients. We aimed to perform a systematic review and meta-analysis of the literature to assess the efficacy and safety of AAV-based gene therapy for hemophilia.
We systematically searched PubMed, Clinical Trials, Medline, Web of Science, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for clinical trials involving patients diagnosed with hemophilia and treated with AAV gene therapy. The outcomes included annualized bleeding rate (ABR), annualized infusion rate (AIR), the incidence of treatment-related adverse events (TRAEs), alanine aminotransferase (ALT) elevation, and aspartate transaminase (AST) elevation.
A total of 13 articles were selected from 879 articles for meta-analysis. Pooled analyses showed that after gene therapy, the ABR was 1.10 and the AIR was 3.92, respectively. At 1 year after AAV gene therapy, all participants exhibited factor activity levels above their baseline values, with the highest level reaching 93.47%. Additionally, 50% of the hemophilia patients had elevated TRAEs, 50% had elevated ALT levels, and 29% had elevated AST levels. We also performed a subgroup analysis of these results according to different haemophilia types, various transgene types, AAV capsids, neutralizing antibody titers, and baseline factor VIII activity.
Our analysis supported the efficacy and safety of AAV-mediated gene therapy for hemophilia, providing a reference for clinical practice and the development of more gene therapy drugs.
通过静脉注射基于腺相关病毒（AAV）的肝脏定向基因疗法，血友病患者已获得显著的临床益处。然而，尚未进行基于血友病类型、各种转基因类型、AAV衣壳、中和抗体滴度和基线因子VIII活性的全面荟萃分析，以评估AAV载体基因疗法对血友病患者的疗效。我们旨在对文献进行系统评价和荟萃分析，以评估基于AAV的基因疗法治疗血友病的疗效和安全性。
我们系统检索了PubMed、临床试验、Medline、科学网、Embase、Cochrane对照试验中心注册库和Cochrane系统评价数据库，以查找涉及诊断为血友病并接受AAV基因疗法治疗的患者的临床试验。结局指标包括年化出血率（ABR）、年化输注率（AIR）、治疗相关不良事件（TRAEs）的发生率、丙氨酸氨基转移酶（ALT）升高和天冬氨酸氨基转移酶（AST）升高。
从879篇文章中总共筛选出13篇文章进行荟萃分析。汇总分析显示，基因治疗后，ABR分别为1.10，AIR为3.92。在AAV基因治疗1年后，所有参与者的因子活性水平均高于其基线值，最高水平达到93.47%。此外，50%的血友病患者TRAEs升高，50%的患者ALT水平升高，29%的患者AST水平升高。我们还根据不同的血友病类型、各种转基因类型、AAV衣壳、中和抗体滴度和基线因子VIII活性对这些结果进行了亚组分析。
我们的分析支持了AAV介导的基因疗法治疗血友病的疗效和安全性，为临床实践和更多基因治疗药物的开发提供了参考。
