Document Type
Article
Peer Reviewed
1
Publication Date
3-1-2018
NLM Title Abbreviation
Haemophilia
Journal/Book/Conference Title
Haemophilia : the official journal of the World Federation of Hemophilia
PubMed ID
29436077
DOI of Published Version
10.1111/hae.13413
Start Page
245
End Page
252
Abstract
INTRODUCTION: Immune tolerance induction (ITI) is the gold standard for eradication of factor VIII inhibitors in severe haemophilia A; however, it usually requires treatment for extended periods with associated high burden on patients and healthcare resources.
AIM: Review outcomes of ITI with recombinant factor VIII Fc fusion protein (rFVIIIFc) in patients with severe haemophilia A and high-titre inhibitors.
METHODS: Multicentre retrospective chart review of severe haemophilia A patients treated with rFVIIIFc for ITI.
RESULTS: Of 19 patients, 7 were first-time ITI and 12 were rescue ITI. Of 7 first-time patients, 6 had at least 1 high-risk feature for ITI failure. Four of 7 first-time patients were tolerized in a median of 7.8 months. The remaining 3 patients continue on rFVIIIFc ITI. Of 12 rescue patients, 7 initially achieved a negative Bethesda titre (≤0.6) in a median of 3.3 months, 1 had a decrease in Bethesda titre and continues on rFVIIIFc ITI and 4 have not demonstrated a decrease in Bethesda titre. Of these 4, 3 continue on rFVIIIFc ITI and 1 switched to bypass therapy alone. Two initially responsive patients transitioned to other factors due to recurrence. Overall, 16 of 19 patients remain on rFVIIIFc (prophylaxis or ITI). For those still undergoing ITI, longer follow-up is needed to determine final outcomes. No adverse events reported.
CONCLUSIONS: Recombinant factor VIII Fc fusion protein demonstrated rapid time to tolerization in high-risk first-time ITI patients. For rescue ITI, rFVIIIFc showed therapeutic benefit in some patients who previously failed ITI with other products. These findings highlight the need to further evaluate the use of rFVIIIFc for ITI.
Keywords
Child, Child, Preschool, Factor VIII, Hemophilia A, Humans, Immunoglobulin Fc Fragments, Infant, Recombinant Fusion Proteins, Retrospective Studies, Pediatrics
Journal Article Version
Version of Record
Rights
© 2018 The Authors. Haemophilia Published by John Wiley & Sons Ltd
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Recommended Citation
Haemophilia. 2018 Mar;24(2):245-252. doi: 10.1111/hae.13413. Epub 2018 Feb 13.
Included in
Circulatory and Respiratory Physiology Commons, Hematology Commons, Medical Genetics Commons, Pediatrics Commons
URL
https://ir.uiowa.edu/pediatrics_pubs/19
Comments
This study was sponsored by Bioverativ Therapeutics, Inc. (Waltham, MA). Medical writing and editorial support were provided by Ashleigh Pulkoski-Gross, PhD (Fishawack Communications, Conshohocken, PA) and Santo D’Angelo, PhD (Fishawack Communications, Conshohocken, PA), which was funded by Bioverativ Therapeutics, Inc. (Waltham, MA).