Recombinant factor VIII Fc fusion protein for immune tolerance induction in patients with severe haemophilia A with inhibitors—A retrospective analysis |
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| Authors: | M. Carcao A. Shapiro J. M. Staber N. Hwang C. Druzgal K. Lieuw M. Belletrutti C. D. Thornburg S. P. Ahuja J. Morales‐Arias J. Dumont G. Miyasato E. Tsao N. Jain S. W. Pipe |
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| Affiliation: | 1. Division of Haematology/Oncology, Department of Paediatrics, Child Health Evaluative Sciences, Research Institute, Hospital for Sick Children, Toronto, ON, Canada;2. Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA;3. University of Iowa Stead Family Children's Hospital, Iowa City, IA, USA;4. Center for Inherited Blood Disorders, Orange, CA, USA;5. University of Virginia Health System, Charlottesville, VA, USA;6. Walter Reed National Military Medical Center, Bethesda, MD, USA;7. University of Alberta Stollery Children's Hospital, Edmonton, AB, Canada;8. Rady Children's Hospital San Diego, San Diego, CA, USA;9. University Hospitals Rainbow Babies and Children's Hospital, Cleveland, OH, USA;10. Bioverativ Therapeutics, Inc., Waltham, MA, USA;11. Trinity Partners LLC, Waltham, MA, USA;12. University of Michigan, Ann Arbor, MI, USA |
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| 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. |
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| Keywords: | haemophilia A immune tolerance induction inhibitor recombinant factor VIII Fc fusion protein rescue therapy retrospective chart review |
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