Emicizumab in tolerized patients with hemophilia A with inhibitors: A single-institution pediatric cohort assessing inhibitor status

• Type of Material: Article
• Authors: Glaivy Batsuli, Emory University; Amanda Greene, Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta; Shannon Meeks, Emory University; Robert Sidonio Jr, Emory University
• Language: English
• Date: 2021-02-08
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2021 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-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/rth2.12475
• Title of Journal or Parent Work: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
• Volume: 5
• Issue: 2
• Start Page: 342
• End Page: 348
• Grant/Funding Information: AG has funding through the National Hemophilia Foundation (NHF) ‐ Nursing Excellence Fellowship
• Keywords: IMMUNE TOLERANCE INDUCTION; Science & Technology; FACTOR-VIII INHIBITORS; hemophilia A; ANTIBODY; Life Sciences & Biomedicine; Peripheral Vascular Disease; immune tolerance; PROPHYLAXIS; REGISTRY; Hematology; PREDICTORS; pediatrics; factor VIII; Cardiovascular System & Cardiology; antibodies
• Research Categories: Health Sciences, Public Health; Health Sciences, Oncology

Abstract

Background: The majority of patients with hemophilia A with inhibitors who undergo immune tolerance induction (ITI) achieve successful tolerance and transition to factor VIII (FVIII) prophylaxis. A portion of these patients have switched to emicizumab for bleeding prevention. However, the risk of inhibitor relapse on emicizumab is unclear. Objective: To evaluate the inhibitor status of patients with hemophilia A and inhibitors who achieved successful/partial tolerance after ITI and transitioned from FVIII prophylaxis to emicizumab. Methods: This is a single-institution, retrospective review of pediatric patients with severe hemophilia A who have completed ITI with FVIII and switched to emicizumab. Results/Conclusions: Seven successfully tolerized and five partially tolerized patients were identified. Three patients continued intermittent FVIII infusions on emicizumab at 50-70 IU/kg twice weekly, once weekly, or every other week due to concerns for inhibitor relapse or loss of recent FVIII tolerance by the treating provider. Eleven of 12 patients (92%) maintained negative inhibitor titers at a mean follow-up of 14.2 ± 6.1 months. One individual had an inhibitor relapse with a peak titer of 2.5 BU/mL. Five of the 11 patients (45%) with negative inhibitor titers had detectable nonneutralizing anti-FVIII IgG4 antibodies, but none of the patients had detectable IgG1 antibodies. There were no inhibitor recurrences in a subset of six patients after FVIII re-exposure for bleeding events or surgery. Given that the presence of an inhibitor significantly impacts factor product choice for bleeding management, ongoing inhibitor monitoring in tolerized patients with hemophilia A who transition to emicizumab is strongly recommended.