Invasive procedures and surgery following etranacogene dezaparvovec gene therapy in people with hemophilia B.

IF 5.5 2区医学 Q1 HEMATOLOGY

Journal of Thrombosis and Haemostasis Pub Date : 2024-09-26 DOI:10.1016/j.jtha.2024.08.027

Niamh O'Connell, Paul van der Valk, Sandra Le Quellec, Esteban Gomez, Paul E Monahan, Shelley E Crary, Michiel Coppens, Richard Lemons, Giancarlo Castaman, Robert Klamroth, Emily Symington, Doris V Quon, Peter Kampmann

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引用次数: 0

Abstract

Background: Little information regarding the management of invasive procedures in people with hemophilia B (HB) after undergoing gene therapy is available. Here, we report the management of invasive procedures in people with severe or moderately severe HB who had previously been treated with etranacogene dezaparvovec in the phase 2b and phase 3 Health Outcomes with Padua Gene; Evaluation in Hemophilia B clinical trials (NCT03489291 and NCT03569891).

Objectives: The objective of this study was to describe the use of exogenous FIX, endogenous FIX activity prior to invasive procedures, and peri- and postoperative bleeds in participants who underwent invasive procedures after receiving etranacogene dezaparvovec gene therapy.

Methods: This retrospective analysis included invasive procedures performed within 3 and 2 years following a single infusion of 2 × 10¹³ gc/kg of etranacogene dezaparvovec in participants in the phase 2b and Health Outcomes with Padua Gene; Evaluation in Hemophilia B trials, respectively. Data for factor (F)IX dosing, duration of postoperative FIX use, FIX activity prior to invasive procedures, and postoperative bleeds were collected and analyzed.

Results: The analysis included 64 procedures in 29 participants: 9 major surgeries, 24 minor surgeries, 11 endoscopies, 3 endoscopies with biopsy/polypectomy, and 17 dental procedures. Uncontaminated endogenous FIX activity corresponded to mild hemophilia or normal levels prior to 98% of all procedures, with a median endogenous FIX activity of 43.8 IU/dL (range, 3.1-113 IU/dL). All major surgeries were managed with exogenous FIX, 67% with ≤4 days of FIX infusion. Most minor surgeries (88%), endoscopies (82%), and dental procedures (94%) were managed with no or a single FIX infusion. Postoperative bleeds occurred after 1 minor surgery and 4 dental procedures. There were no symptomatic thrombotic events or FIX inhibitor developments.

Conclusion: Etranacogene dezaparvovec has the potential to facilitate perioperative management in people with HB by reducing the need for perioperative exogenous FIX and its associated risks.

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血友病 B 患者接受 etranacogene dezaparvovec 基因治疗后的侵入性程序和手术。

背景：有关血友病 B（HB）患者接受基因治疗后侵入性程序管理的信息很少。在此，我们报告了曾在 2b 期和 3 期 HOPE-B 临床试验（NCT03489291、NCT03569891）中接受 etranacogene dezaparvovec 治疗的重度或中度 HB 患者的侵入性手术管理情况：这项回顾性分析包括分别在 2b 期和 HOPE-B 期临床试验参与者单次输注 2x1013 gc/kg etranacogene dezaparvovec 后 3 年和 2 年内进行的侵入性手术。收集并分析了FIX剂量、术后使用FIX的持续时间、侵入性手术前的FIX活性以及术后出血等数据：分析包括 29 名参与者的 64 项手术：9 项大手术、24 项小手术、11 项内窥镜手术、3 项带活检/息肉切除术的内窥镜手术和 17 项牙科手术。在 98% 的手术前，未受污染的内源性 FIX 活性相当于轻度血友病或正常水平，内源性 FIX 活性中位数为 43.8 IU/dL（范围为 3.1-113 IU/dL）。所有大手术都使用外源性 FIX，67% 的手术输注 FIX 的时间少于 4 天。大多数小手术（88%）、内窥镜手术（82%）和牙科手术（94%）无需输注或只需输注一次 FIX。在一次小手术和四次牙科手术后发生了术后出血。没有出现无症状血栓事件或FIX抑制剂不良反应：结论：Etranacogene dezaparvovec 有可能减少围手术期外源性 FIX 的需求及其相关风险，从而促进 HB 患者的围手术期管理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Thrombosis and Haemostasis 医学-外周血管病

CiteScore

24.30

自引率

3.80%

发文量

321

审稿时长

1 months

期刊介绍： The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.