Zeyu Han, Xianyanling Yi, Jin Li, Dazhou Liao, Guangping Gao, Jianzhong Ai
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A total of 12 articles from 11 clinical trials were selected from 868 articles for meta-analysis. Pooled analyses showed that AAV-based gene therapy in hemophilia patients reduced the number of bleeding events and the number of factor infusion events by an approximate average of 7 per year and 103 per year, respectively. Eighty percent, 18%, and 63% of hemophilia patients had elevated TRAE, SAE, and ALT levels, respectively. Moreover, subgroup analysis found a significant reduction in ABR and AIR 2-3 years after the therapy. Additional findings that were not pooled including coagulation factor activity are presented in the accompanying tables. 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引用次数: 0
摘要
近年来,基于腺相关病毒(AAV)的基因疗法临床试验取得了显著进展。我们旨在对文献进行系统回顾和荟萃分析,以评估基于 AAV 的血友病基因疗法的有效性和安全性。我们在 Web of Science、Embase、PubMed 和 Cochrane 系统综述数据库中系统地检索了涉及确诊为血友病并接受 AAV 介导的基因治疗的患者的临床试验。我们提取了年出血率(ABR)、年输液率(AIR)以及治疗相关不良事件(TRAE)、严重不良事件(SAE)和丙氨酸氨基转移酶(ALT)升高的发生率等数据作为研究结果。从 868 篇文章中筛选出 11 项临床试验中的 12 篇文章进行荟萃分析。汇总分析表明,基于 AAV 的血友病基因疗法可减少血友病患者的出血次数和因子输注次数,平均每年分别减少约 7 次和 103 次。分别有 80%、18% 和 63% 的血友病患者 TRAE、SAE 和 ALT 水平升高。此外,亚组分析发现,治疗 2-3 年后,ABR 和 AIR 显著下降。其他未汇总的结果(包括凝血因子活性)见附表。我们的分析证实了 AAV 介导的血友病基因疗法的有效性和安全性,为将来将其作为一种治疗方法广泛应用于血友病患者的临床治疗提供了证据。
Efficacy and Safety of Adeno-Associated Virus-Based Clinical Gene Therapy for Hemophilia: A Systematic Review and Meta-Analysis.
Clinical trials of adeno-associated virus (AAV)-based gene therapy have made remarkable progress in recent years. 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 the Web of Science, Embase, PubMed, and the Cochrane Database of Systematic Reviews databases, for clinical trials involving patients diagnosed with hemophilia and treated with AAV-mediated gene therapy. Data on the annualized bleeding rate (ABR), annualized infusion rate (AIR), the incidence of treatment-related adverse events (TRAEs), severe adverse events (SAEs), and alanine aminotransferase (ALT) elevation were extracted as our outcomes. A total of 12 articles from 11 clinical trials were selected from 868 articles for meta-analysis. Pooled analyses showed that AAV-based gene therapy in hemophilia patients reduced the number of bleeding events and the number of factor infusion events by an approximate average of 7 per year and 103 per year, respectively. Eighty percent, 18%, and 63% of hemophilia patients had elevated TRAE, SAE, and ALT levels, respectively. Moreover, subgroup analysis found a significant reduction in ABR and AIR 2-3 years after the therapy. Additional findings that were not pooled including coagulation factor activity are presented in the accompanying tables. Our analysis supported the efficacy and safety of AAV-mediated gene therapy for hemophilia, providing evidence for its application as a therapeutic option for widespread clinical use in hemophilia patients in the future.
期刊介绍:
Human Gene Therapy is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes in-depth coverage of DNA, RNA, and cell therapies by delivering the latest breakthroughs in research and technologies. Human Gene Therapy provides a central forum for scientific and clinical information, including ethical, legal, regulatory, social, and commercial issues, which enables the advancement and progress of therapeutic procedures leading to improved patient outcomes, and ultimately, to curing diseases.