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| Major Dental Surgeries Conducted Under Fitusiran Prophylaxis in People With Hemophilia A and B, With and Without Inhibitors Suchitra S Acharya1, Laurent Frenzel2, Kaan Kavakli3, Teh-Liane Khoo4, László Nemes5, Jing Sun6, Te-Fu Weng7, Chur-Woo You8, Salim Kichou9, Abhimanyu Yarramaneni10, Laurel A Menapace10, Yuqian Shen10, Ezio Zanon11. 1Northwell Health, New York, NY, USA.2Groupe Hospitalier Necker Enfants Malades, Paris, France.3Ege University Faculty of Medicine, Izmir, Turkey.4Royal Prince Alfred Hospital, Sydney, Australia.5Central Hospital of Northern Pest – Military Hospital, Budapest, Hungary.6Nanfang Hospital, Guangzhou, China.7Chung Shan Medical University Hospital, Taichung, Taiwan.8Eulji University Hospital, Daejeon, South Korea.9Sanofi Genzyme, Paris, France.10Sanofi, Cambridge, MA, USA.11Azienda Ospedale Università di Padova, Padua, Italy |
Abstract
Introduction As there is an increasing number of approved non-factor therapies in the changing hemophilia treatment landscape, an ongoing unmet need remains for data regarding the perioperative management utilizing these therapeutics. Fitusiran is an antithrombin (AT)-lowering therapeutic that increases thrombin generation to restore hemostasis in people with hemophilia (PwH) A/B, with or without inhibitors. In the Phase 3 open-label extension study ATLAS-OLE (NCT03754790), the AT-based dose regimen (AT-DR; targeting AT levels of 15–35%) was well tolerated while maintaining clinically meaningful bleed protection. Breakthrough bleed management guidelines (BMG) with reduced dose and frequency of clotting factor concentrates (CFC)/bypassing agents (BPA) were implemented for perioperative management (Table 1). Here we describe hemostatic outcomes and provide case reviews of dental surgeries performed in PwHA/B aged ≥12 years receiving fitusiran prophylaxis, regardless of inhibitor status. Methods All major dental surgeries in the fitusiran clinical development program as of 14 June 2023 were evaluated, including participants on the AT-DR and fixed 80 mg once-monthly dose. Procedures conducted during fitusiran prophylaxis with AT activity levels <60% were included. Major dental surgery was defined as extraction of molar teeth or ≥3 non-molar teeth, or tooth implantation. Procedure management was at investigator/surgeon’s discretion. Perioperative hemostatic control was assessed based on the ISTH 4-point response scale (excellent/good/moderate/poor) on the day of surgery. Results Nineteen major dental surgeries were performed in 16 participants (including four participants with inhibitors) during the clinical development program (Table 2). Twelve surgeries were conducted with the AT-DR and seven surgeries were conducted with the fixed 80 mg dose. Hemostatic control was good/excellent in 100% (n=10/10) of dental surgeries with a hemostatic assessment available on the day of the surgery. Adherence to BMG was 78.9% (n=15/19) for dental surgeries. Three dental surgeries were conducted without any CFC/BPA (molar and wisdom teeth extractions); none required blood components, and no excessive blood loss or complications were reported in the perioperative period. AT concentrate (ATIII) was not used in any major dental surgery. Tranexamic acid, an antifibrinolytic, was administered during four (21%) major dental surgeries. In two cases, it was given for one day with ≤2 doses each; in the other two, it was administered for >7 days. No new safety concerns were identified, and no events of postoperative thrombosis were reported in participants undergoing major dental surgery with fitusiran prophylaxis. Conclusion Major dental surgeries can be safely and effectively performed in PwHA/B, with and without inhibitors, receiving fitusiran prophylaxis using reduced CFCs/BPA doses, as per BMG, highlighting the benefit of reduced CFC/BPA consumption with fitusiran prophylaxis. Reversal of the effects of fitusiran with administration of ATIII is not necessary.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.