Untreated bleeds in people with hemophilia A in a noninterventional study and intrapatient comparison after initiating emicizumab in HAVEN 1-3

• Type of Material: Article
• Authors: Michael U Callaghan, Central Michigan University; Elina Asikanius, F. Hoffmann‐La Roche Ltd; Michaela Lehle, F. Hoffmann‐La Roche Ltd; Johannes Oldenburg, University of Bonn; Johnny Mahlangu, University of Witwatersrand; Marianne Uguen, F. Hoffmann‐La Roche Ltd; Sammy Chebon, F Hoffmann La Roche Ltd; Rebecca Kruse-Jarres, University of Washington; Victor Jiménez‐Yuste, Autónoma University; Midori Shima, Nara Medical University; Peter Trask, Genentech Inc; Christine Kempton, Emory University; Craig M Kessler, Georgetown University Hospital; Gallia G Levy, Genentech Inc; Flora Peyvandi, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
• Language: English
• Date: 2022-08-01
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/rth2.12782
• Title of Journal or Parent Work: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
• Volume: 6
• Issue: 6
• Start Page: e12782
• End Page: e12782
• Grant/Funding Information: The study was funded by F. Hoffmann‐La Roche Ltd and Chugai Pharmaceutical Co., Ltd.
• Keywords: prophylaxis; Hematology; MANAGEMENT; bleeding; Science & Technology; Cardiovascular System & Cardiology; hemophilia A; hemostasis; Peripheral Vascular Disease; PROPHYLAXIS; TRIALS; factor VIII; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

Background: Bleeding in people with hemophilia A can be life threatening, and intra-articular bleeds can result in joint damage. Most clinical studies focus on treated bleeds, while bleeds not treated with coagulation factor(s) (untreated bleeds) are underreported. Objectives: We assessed the incidence of untreated bleeds during a noninterventional study (NIS) wherein people with hemophilia A, with or without factor VIII (FVIII) inhibitors, were managed according to standard practice. Patients/Methods: Using the Bleed and Medication Questionnaire, we prospectively collected data from three cohorts: Cohort A, adults/adolescents (age ≥12 years) with FVIII inhibitors; Cohort B, children (aged <12 years) with FVIII inhibitors; Cohort C, adults/adolescents without FVIII inhibitors. Untreated bleeds were analyzed for site, frequency, and etiology of bleeding and compared with those during emicizumab prophylaxis in the same individuals after transferring to a Phase III HAVEN trial. Results: In the 221 participants enrolled in the NIS (Cohort A, n = 103; Cohort B, n = 24; Cohort C, n = 94), the incidence of untreated bleeds was approximately 40% of all bleeds in people with FVIII inhibitors and 26.2% in adolescents/adults without inhibitors. Approximately 70% of treated bleeds and approximately 54% of untreated bleeds in adults/adolescents were in joints. Untreated joint bleeds were less common (7.1%) in children. Overall, intra-individual comparisons showed reduced treated/untreated bleeds following transition from standard to emicizumab prophylaxis. Conclusion: A significant proportion of bleeding events are untreated in people with hemophilia A. There is a need to further understand why bleeds remain untreated and to capture such events in clinical studies.