O'Connell Niamh, van der Valk Paul, Le Quellec Sandra, Gomez Esteban, Monahan Paul E, Crary Shelley E, Coppens Michiel, Lemons Richard, Castaman Giancarlo, Klamroth Robert, Symington Emily, Quon Doris V, Kampmann Peter
National Coagulation Centre, St. James's Hospital, Dublin, Ireland; School of Medicine, Trinity College, Dublin, Ireland.
Van Creveldkliniek, Department of Benign Hematology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
J Thromb Haemost. 2025 Jan;23(1):73-84. doi: 10.1016/j.jtha.2024.08.027. Epub 2024 Sep 26.
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).
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.
This retrospective analysis included invasive procedures performed within 3 and 2 years following a single infusion of 2 × 10 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.
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.
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.
关于接受基因治疗后的B型血友病（HB）患者侵入性操作管理的信息较少。在此，我们报告了在2b期和3期帕多瓦基因健康结局；B型血友病评估临床试验（NCT03489291和NCT03569891）中，先前接受依特那考基因德扎帕罗韦治疗的重度或中度重度HB患者的侵入性操作管理情况。
本研究的目的是描述在接受依特那考基因德扎帕罗韦基因治疗后接受侵入性操作的参与者中，外源性FIX的使用、侵入性操作前的内源性FIX活性以及围手术期和术后出血情况。
这项回顾性分析分别纳入了在2b期试验和帕多瓦基因健康结局；B型血友病评估试验中，单次输注2×10 gc/kg依特那考基因德扎帕罗韦后3年和2年内进行的侵入性操作。收集并分析了因子（F）IX剂量、术后FIX使用持续时间、侵入性操作前的FIX活性以及术后出血的数据。
分析包括29名参与者的64项操作：9项大手术、24项小手术、11项内镜检查、3项伴有活检/息肉切除术的内镜检查以及17项牙科操作。在所有操作的98%之前，未受污染的内源性FIX活性对应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）。所有大手术均采用外源性FIX进行管理，67%的患者FIX输注时间≤4天。大多数小手术（88%）、内镜检查（82%）和牙科操作（94%）无需FIX输注或仅进行单次FIX输注。1项小手术和4项牙科操作后发生了术后出血。未出现有症状的血栓事件或FIX抑制剂形成。
依特那考基因德扎帕罗韦有可能通过减少围手术期外源性FIX的需求及其相关风险，促进HB患者的围手术期管理。
