Inhibitor recurrence after immune tolerance induction: a multicenter retrospective cohort study

• Type of Material: Article
• Authors: A. Antun, Emory University; P.E. Monahan, University of North Carolina; M.J. Manco-Johnson, University of Colorado; M.U. Callaghan, Children's Hospital of Michigan; M. Kanin, University of Southern California; C. Knoll, Phoenix Children's Hospital; S.L. Carpenter, Children's Mercy Hospital; J.A. Davis, University of Miami; M.F. Guerrera, Children's National Medical Center; R. Kruse-Jarres, Tulane University; M.V. Ragni, University of Pittsburgh; C. Witmer, Children's Hospital of Philadelphia; C.E. McCracken, Emory University; Christine Kempton, Emory University
• Language: English
• Date: 2015-11-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 International Society on Thrombosis and Haemostasis.
• Final Published Version (URL): http://dx.doi.org/10.1111/jth.13143
• Title of Journal or Parent Work: Journal of Thrombosis and Haemostasis
• ISSN: 1538-7933
• Volume: 13
• Issue: 11
• Start Page: 1980
• End Page: 1988
• Grant/Funding Information: This study was funded by an investigator-initiated grant from Novo Nordisk, Inc. (CLK) and by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454 (AA).
• Keywords: hemophilia; F8; prophylaxis; Hematology; immune tolerance; recurrence; Life Sciences & Biomedicine; MUTATIONS; Cardiovascular System & Cardiology; FACTOR-VIII GENE; Science & Technology; PREDICTORS; Peripheral Vascular Disease; incidence
• Research Categories: Health Sciences, Immunology; Health Sciences, Medicine and Surgery

Abstract

Background: Immune tolerance induction (ITI) in patients with congenital hemophilia A is successful in up to 70%. Although there is growing understanding of predictors of response to ITI, the probability and predictors of inhibitor recurrence following successful ITI are not well understood. Objectives: To determine the association of clinical characteristics, particularly adherence to FVIII prophylaxis following ITI, with inhibitor recurrence in patients with hemophilia A who were considered tolerant following ITI. Methods: In this multicenter retrospective cohort study, 64 subjects with FVIII level <2% who were considered successfully tolerant following ITI were analyzed to estimate the cumulative probability of inhibitor recurrence using the Kaplan-Meier method. The association of clinical characteristics with inhibitor recurrence was assessed using logistic regression. Results: A recurrent inhibitor titer ≥ 0.6 BU/ml occurred at least once in 19 (29.7%) and more than once in 12 (18.8%). The probability of any recurrent inhibitor at 1 and 5 years was 12.8% and 32.5% respectively. Having a recurrent inhibitor was associated with having received immune modulation during ITI (OR 3.8, 95% CI: 1.2-22.4) and FVIII recovery of <85% at the end of ITI (OR 2.6, 95% CI: 1.3-5.9), but was not associated with adherence to post-ITI prophylactic FVIII infusion (OR=0.5, 95% CI: 0.06-4.3). Conclusions: The use of immune modulation therapy during ITI and lower FVIII recovery at the end of ITI appear to be associated with an increased risk of inhibitor recurrence following successful ITI. Adherence to post-ITI prophylactic FVIII infusions is not a major determinant of recurrence.