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

Autor:	O'Connell N; National Coagulation Centre, St. James's Hospital, Dublin, Ireland; School of Medicine, Trinity College, Dublin, Ireland. Electronic address: noconnell@stjames.ie., van der Valk P; Van Creveldkliniek, Department of Benign Hematology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Le Quellec S; CSL Behring, King of Prussia, Pennsylvania, USA., Gomez E; The Center for Inherited Blood Disorders, Orange, California, USA., Monahan PE; CSL Behring, King of Prussia, Pennsylvania, USA., Crary SE; Department of Pediatrics, Hematology and Oncology, Arkansas Children's Hospital, Little Rock, Arkansas, USA., Coppens M; Department of Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension & Thrombosis, Amsterdam, The Netherlands., Lemons R; Pediatric Hematology-Oncology, University of Utah and Primary Children's Hospital, Salt Lake City, Utah, USA., Castaman G; Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy., Klamroth R; Internal Medicine - Angiology and Hemostaseology, Vivantes Klinikum, Berlin, Germany., Symington E; Cambridge University Hospitals, Cambridge, United Kingdom., Quon DV; Orthopaedic Hemophilia Treatment Center, Los Angeles, California, USA., Kampmann P; Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2024 Sep 26. Date of Electronic Publication: 2024 Sep 26.
DOI:	10.1016/j.jtha.2024.08.027
Abstrakt:	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 × 10 13 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. Competing Interests: Declaration of competing interests N.O. has received financial support for research from Sobi; received consultancy fees from F. Hoffmann-La Roche Ltd, uniQure, Sobi, and CSL Behring; and is a member of Speakers Bureaus for F. Hoffmann-La Roche Ltd, Sobi, CSL Behring, Takeda, Bayer, and Novo Nordisk. All fees are donated to an institutional charitable body that supports education in hemostasis and thrombosis. P.v.d.V. has received consultancy fees from Bayer. E.G. is a member of the Global Blood Therapeutics Speaker Bureau and has received consultant fees from CSL Behring. P.E.M. is an employee of CSL Behring. S.L.Q. is an employee of CSL Behring. S.E.C. has received consultancy fees from Novartis for service on a data safety monitoring board and has received payment for service on advisory boards from Pfizer, Sanofi, and Medexus. M.C. has received financial support for research from Anthos, Bayer, CSL Behring, Novo Nordisk, and Hoffmann-La Roche and honoraria for lecturing or consultancy from Alexion, CSL Behring, Daiichi Sankyo, Sanofi, Spark Therapeutics, Octapharma, Pfizer, Sobi, and Viatris. All funds were received by his institution. Nonfinancial conflicts of interest include being a member of the gene therapy working group of the European Association for Haemophilia and Allied Disorders (EAHAD) and a member of the European Reference Network (ERN) EuroBloodNet. R.L. has received fees for consulting, advisory boards, and speakers’ bureaus from CSL Behring, Pfizer, and Novo Nordisk. G.C. has received financial support for research from CSL Behring, Pfizer, and Sobi; has consulted for and received honoraria from Bayer, Roche, Sobi, Grifols, Novo Nordisk, Werfen, and Kedrion; and was a member of the Board of Directors or advisory committees for Ablynx, Alexion, Bayer, LFB, Takeda, CSL Behring, Novo Nordisk, Pfizer, Roche, Sanofi, Sobi, and uniQure. R.K. has received honoraria from and/or been a member of advisory committees for Bayer, BioMarin, Biotest, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche/Chugai, Sanofi, Sobi, and Takeda. E.S. has received support for attending conferences from CSL Behring, Roche, and Novo Nordisk. D.V.Q. has received fees for consulting/advisory boards/speakers bureaus from Bayer, BioMarin, CSL Behring, Genentech/Roche, Novo Nordisk, Pfizer, Sanofi, and Takeda. P.K. has received consultancy fees from BioMarin, CSL Behring, Novo Nordisk, Takeda, and uniQure. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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