M Carcao1, A Shapiro2, J M Staber3, N Hwang4, C Druzgal5, K Lieuw6, M Belletrutti7, C D Thornburg8, S P Ahuja9, J Morales-Arias10, J Dumont10, G Miyasato11, E Tsao10, N Jain10, S W Pipe12. 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.
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.
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 Apatients 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.
Authors: Katalin Kis-Toth; Gaurav Manohar Rajani; Allison Simpson; Kate L Henry; Jennifer Dumont; Robert T Peters; Joe Salas; Christine Loh Journal: Blood Adv Date: 2018-11-13
Authors: Michal Pyzik; Kine M K Sand; Jonathan J Hubbard; Jan Terje Andersen; Inger Sandlie; Richard S Blumberg Journal: Front Immunol Date: 2019-07-10 Impact factor: 7.561
Authors: Maria T Georgescu; Paul C Moorehead; Tongyao Liu; Jennifer Dumont; David W Scott; Christine Hough; David Lillicrap Journal: Front Immunol Date: 2020-02-07 Impact factor: 7.561