Document Type

Article

Peer Reviewed

1

Publication Date

2-13-2018

NLM Title Abbreviation

Haemophilia

Journal/Book/Conference Title

Haemophilia

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

Granting or Sponsoring Agency

Bioverativ Therapeutics, Inc.

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).

Journal Article Version

Version of Record

Published Article/Book Citation

Haemophilia. 2018 Mar;24(2):245-252. doi: https://doi.org/10.1111/hae.13413

Rights

© 2018 The Authors

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

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URL

https://ir.uiowa.edu/pediatrics_pubs/19