Eradication of Factor VIII Inhibitors in Patients with Mild and Moderate Hemophilia A

• Type of Material: Article
• Authors: Christine Kempton, Emory University; Geoff Allen, Brown University; Jeffrey Hord, Akron Children’s Hospital; Rebecca Kruse-Jarres, Tulane University; Rajiv K. Pruthi, Mayo Clinic; Christopher Walsh, Mount Sinai Medical Center; Guy Young, Children’s Hospital Los Angeles; John M. Soucie, Emory University
• Language: English
• Date: 2012-09
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Wiley Periodicals, Inc.
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/ajh.23269/abstract
• Title of Journal or Parent Work: American Journal of Hematology
• ISSN: 0361-8609
• Volume: 87
• Issue: 9
• Start Page: 933
• End Page: 936
• Grant/Funding Information: The analysis and writing represented in this article was supported by a grant from CSL Behring Foundation for Advancement of Patient Health (C.K.) and the Cooperative Agreement Prevention of Bleeding Disorder Complications through Regional Hemophilia Treatment Centers. C.K. also receives research support from NHLBI (1K23HL105785-01).
• Keywords: Immunotherapy; Hemophilia A
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

In hemophilia A, up to 25% of new anti-factor VIII (FVIII) inhibitory antibodies (inhibitors) occur in patients with mild or moderate disease [1]. Once the inhibitor develops, options for management include observation, immune modulation, and immune tolerance induction (ITI). Currently, there is little data to guide a clinician’s management decisions. In a case series, 8/26 subjects with mild or moderate hemophilia complicated by an inhibitor underwent ITI; 2 successful, 2 unsuccessful and 4 partially successful [2]. In a systematic review of the literature, 12/16 patients with mild or moderate hemophilia responded to rituximab for treatment to eradicate the inhibitor [3]. To increase our understanding of treatment options for inhibitor eradication in patients with mild or moderate hemophilia A complicated by an inhibitor, a secondary analysis of clinical and treatment characteristics in a cohort of 36 patients with mild or moderate hemophilia A and inhibitor was undertaken. In multivariate analyses, rituximab alone (n=6) and other immune modulating treatments alone (n=2) were significantly associated with an increased likelihood of inhibitor clearance [hazard ratio (HR) of 4.4 (95% CI 1.06–20.03) and 10.21 (95% CI 1.17–78.28), respectively] whereas ITI alone (n=9) was not [HR 1.35 (95% CI 0.44–4.07)].