Real‐world prophylactic usage of recombinant factor VIII Fc in Sweden: A report from the Swedish national registry for bleeding disorders

Haemophilia ◽  
2021 ◽  
Author(s):  
Margareta Holmström ◽  
Elsa Olsson ◽  
Jan Astermark ◽  
Malin Axelsson ◽  
Anna Olsson ◽  
...  
Keyword(s):  
Factor Viii ◽  
Real World ◽  
National Registry ◽  
Recombinant Factor Viii ◽  
Bleeding Disorders

scholarly journals Real-World Health Care Expenditure In Hemophilia A Patients Using Standard And Extended Half-Life Recombinant Factor VIII Products

2017 ◽  
Vol 20 (9) ◽  
pp. A567
Author(s):  
D Spurden ◽  
PF Fogarty ◽  
A Chhabra ◽  
BJ Tortella ◽  
J Alvir ◽  
...  
Keyword(s):  
Health Care ◽  
Factor Viii ◽  
Real World ◽  
Half Life ◽  
Hemophilia A ◽  
Health Care Expenditure ◽  
Recombinant Factor Viii ◽  
World Health

scholarly journals Real-World Experience Using Emicizumab Prophylaxis for Hemophilia a: Single-Center Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 36-36
Author(s):  
Anshul Vagrecha ◽  
Joseph Stanco ◽  
Daphenee Ulus ◽  
Suchitra Acharya
Keyword(s):  
Factor Viii ◽  
Board Of Directors ◽  
Knee Arthroplasty ◽  
Real World ◽  
Hemophilia A ◽  
Recombinant Factor Viii ◽  
Phase Iii ◽  
Advisory Committees ◽  
Fviii Inhibitor ◽  
Bypassing Agents

INTRODUCTION: Emicizumab is a recombinant humanized bispecific antibody that mimics Factor VIII by bridging Factor IXa and X. It is an important breakthrough in the therapeutic armamentarium for Hemophilia A. Recently concluded Phase III HAVEN trials demonstrated that prophylaxis with emicizumab is superior to recombinant Factor VIII (rFVIII). Patients with Hemophilia A with inhibitors had a 79% reduction in the Annualized Bleeding Rate (ABR) while on emicizumab prophylaxis vs other bypassing agents. Patients without inhibitors had a 68% reduction in ABR on emicizumab vs rFVIII prophylaxis. However, there is limited data on its use in the post-marketing era. METHODS: We report our experience with emicizumab in children and adults with Hemophilia A with and without inhibitors at a single Hemophilia Treatment Center. This Northwell IRB approved retrospective analysis (Jan 2017 - Jun 2020) included data from 12 months prior to starting emicizumab prophylaxis RESULTS: A total of 38 patients on emicizumab prophylaxis were included. 35 patients (92.1%) had severe and 3 (7.9%) had moderate Hemophilia A. 11 patients (28.9%) had a FVIII inhibitor. The mean age was 16.4 yrs with 18 patients (47%) below the age of 12 (age limit used in HAVEN trials). 54.1% of patients were Caucasian, 18.9% were Asian and 16.2% were African American. Thirty patients (78.9%) were on prophylaxis with either rFVIII (71.5%) or FEIBA (21.4%) before starting emicizumab. All 38 patients were started on emicizumab with a loading dose of 3 mg/kg once weekly for 4 weeks followed by a maintenance dose of 1.5 mg/kg weekly. The ABR decreased by 52% for inhibitor patients (3.6 events before and 1.7 events after starting emicizumab). Similarly, there was a dramatic 70.6% reduction for non-inhibitor patients (1.5 events before and 0.44 events after starting emicizumab). Patients on emicizumab prophylaxis experienced 35 bleeding events over 24 months. Nine out of these 35 events occurred in one patient alone with a high titer FVIII inhibitor. 56.5% of these events were joint bleeds, 26.1% (muscle bleeds), 13% (soft tissue bleeds) and 4.4% were mucocutaneous bleeds. Barring 2 events, all episodes (93.9%) were managed outpatient. A majority of these bleeds (72.1%) in inhibitor patients were treated with recombinant Factor VIIa (rVIIa, 16-24 doses for documented hemarthroses) and 3.4% were treated with FEIBA after nonresponse to rVIIa (9-15 doses) due to delayed treatment. Remaining non -inhibitor patients were treated with rFVIII (2-5 doses) with a good response. 52 % of these bleeds were trauma-related. Five surgeries were conducted in the inhibitor patients while on emicizumab prophylaxis and none experienced perioperative bleeding. RVIIa was used as a bypassing agent for 2 of these surgeries - a hemispherectomy and a port removal. No bypassing agent was used for the remaining 3 port removals. Five surgeries (1 total knee arthroplasty and 4 port removals) were performed in patients without a FVIII inhibitor. Recombinant Factor VIII was used as the replacement agent and the patient with knee arthroplasty experienced post-operative bleeding. There were no thrombotic episodes or deaths and all but one continued on emicizumab. The patient post knee arthroplasty discontinued emicizumab after recurrent bleeds into the replaced joint despite aggressive replacement with rFVIII and absence of an inhibitor. DISCUSSION: We report a real-world experience on the use of emicizumab prophylaxis for Hemophilia A with and without inhibitors in children and adults with 78.9% of our cohort below the age of 21 years. Our study demonstrated a similar decrease in ABR for non-inhibitor patients comparable to the HAVEN clinical trials. However, our inhibitor patients experienced a lower bleed reduction rate on emicizumab and all patients still experienced a considerable number of trauma-related bleeds (likely due to increased participation of inhibitor patients in sports). Two patients with traumatic muscle/joint bleeds were treated with aPCC due to non-response to rVIIa suggesting the need for early treatment of suspected bleeds on emicizumab. No thrombotic events or thrombotic microangiopathy was observed in our patient cohort. Our data suggest the need for ongoing patient education for early bleed recognition on emicizumab prophylaxis, prompt treatment of breakthrough bleeds and pre-sports prophylaxis with FVIII or bypassing agents. Disclosures Acharya: BPL: Membership on an entity's Board of Directors or advisory committees; Novonordisk: Membership on an entity's Board of Directors or advisory committees; Bayer Pharma Inc.: Research Funding.

Measurement of factor VIII activity of B-domain deleted recombinant factor VIII

2001 ◽  
Vol 38 (2, Suppl 4) ◽  
pp. 13-23 ◽  
Author(s):  
M. Mikaelsson ◽  
U. Oswaldsson ◽  
M. A. Jankowski
Keyword(s):  
Factor Viii ◽  
Recombinant Factor Viii ◽  
Factor Viii Activity

A Multicenter Pharmacosurveillance Study for the Evaluation of the Efficacy and Safety of Recombinant Factor VIII in the Treatment of Patients with Hemophilia A

1997 ◽  
Vol 78 (05) ◽  
pp. 1352-1356 ◽  
Author(s):  
Emel Aygören-Pürsün ◽  
Inge Scharrer ◽  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Parvovirus B19 ◽  
Subjective Evaluation ◽  
Recombinant Factor Viii ◽  
Fviii Inhibitor ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Bleeding Episodes ◽  
Recombinant Fviii

SummaryIn this open multicenter study the safety and efficacy of recombinant factor VIII (rFVIII) was assessed in 39 previously treated patients with hemophilia A (factor VIII basal activity ≤15%).Recombinant FVIII was administered for prophylaxis and treatment of bleeding episodes and for surgical procedures. A total of 3679 infusions of rFVIII were given. Efficacy of rFVIII as assessed by subjective evaluation of response to infusion and mean annual consumption of rFVIII was comparable to that of plasma derived FVIII concentrates. The incremental recovery of FVIII (2.4 ± 0,83%/IU/kg, 2.12 ± 0.61%/IU/kg, resp.) was within the expected range. No clinical significant FVIII inhibitor was detected in this trial. Five of 16 susceptible patients showed a seroconversion for parvovirus B19. However, the results are ambiguous in two cases and might be explained otherwise in one further case. Thus, in two patients a reliable seroconversion for parvovirus B19 was observed.

Anti-apoptotic genes Aven and E1B-19K enhance performance of BHK cells engineered to express recombinant factor VIII in batch and low perfusion cell culture

2007 ◽  
Vol 98 (4) ◽  
pp. 825-841 ◽  
Author(s):  
Toey Nivitchanyong ◽  
Amanda Martinez ◽  
Adiba Ishaque ◽  
John E. Murphy ◽  
Konstantin Konstantinov ◽  
...  
Keyword(s):  
Cell Culture ◽  
Factor Viii ◽  
Recombinant Factor Viii ◽  
Perfusion Cell Culture ◽  
Bhk Cells ◽  
Apoptotic Genes

scholarly journals Long‐term safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in subjects with haemophilia A

Haemophilia ◽  
2015 ◽  
Vol 22 (1) ◽  
pp. 72-80 ◽  
Author(s):  
B. Nolan ◽  
J. Mahlangu ◽  
D. Perry ◽  
G. Young ◽  
R. Liesner ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Factor Viii ◽  
Recombinant Factor Viii ◽  
Haemophilia A ◽  
Safety And Efficacy ◽  
Fc Fusion Protein

TT virus contaminates first-generation recombinant factor VIII concentrates

Blood ◽  
2001 ◽  
Vol 98 (8) ◽  
pp. 2571-2573 ◽  
Author(s):  
Alberta Azzi ◽  
Riccardo De Santis ◽  
Massimo Morfini ◽  
Krystyna Zakrzewska ◽  
Roberto Musso ◽  
...  
Keyword(s):  
Factor Viii ◽  
First Generation ◽  
Second Generation ◽  
Human Albumin ◽  
Factor Ix ◽  
Recombinant Factor Viii ◽  
Tt Virus ◽  
Recombinant Product ◽  
Before And After ◽  
Factor Viii Concentrates

Abstract Recombinant factor VIII and factor IX concentrates, human-plasma–derived albumin, and samples from previously untreated patients with hemophilia were examined for the presence of TT virus (TTV) by using polymerase chain reaction testing. Blood samples from the patients were obtained prospectively before and every 3 to 6 months after therapy was begun. TTV was detected in 23.5% of the recombinant-product lots and 55.5% of the albumin lots tested. Only first-generation factor VIII recombinant concentrates stabilized with human albumin were positive for TTV, whereas all second-generation (human protein–free) concentrates were negative for the virus. In 59% of patients treated with either first- or second-generation recombinant factor concentrates, TTV infection developed at some point after the initial infusion. Infection with TTV in these patients before and after treatment did not appear to be clinically important. Thus, first-generation recombinant factor VIII concentrates may contain TTV and the source of the viral contamination may be human albumin.

Sign in / Sign up

Export Citation Format

Share Document