scholarly journals Perioperative Management of Hemophilia A Using Recombinant Factor VIII in Patients Undergoing Major or Minor Surgery

2019 ◽  
Author(s):  
Atsushi Okamoto ◽  
Kenta Yamamoto ◽  
Go Eguchi ◽  
Yoshitaka Kanai ◽  
Terufumi Yamaguchi ◽  
...  
Keyword(s):  
Factor Viii ◽  
Perioperative Management ◽  
Hemophilia A ◽  
Recombinant Factor Viii ◽  
Minor Surgery

An Evaluation of Safety with an Extended Half-Life, Pegylated, Full-Length Recombinant Factor VIII (BAX 855) in the Treatment of 243 Patients with Hemophilia a

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3801-3801
Author(s):  
Werner Engl ◽  
Lisa Patrone ◽  
Dyck-Jones Jacqueline ◽  
Srilatha D. Tangada ◽  
Brigitt E. Abbuehl
Keyword(s):  
Factor Viii ◽  
Safety Profile ◽  
Half Life ◽  
Perioperative Management ◽  
Hemophilia A ◽  
Recombinant Factor Viii ◽  
Employment Equity ◽  
Equity Ownership ◽  
Inhibitory Antibodies

Abstract BAX 855 is an extended half-life, pegylated full-length recombinant factor VIII (PEG-rFVIII) built on ADVATE and is approved for prophylaxis and the treatment of bleeding in hemophilia A. Safety data from 7 clinical studies were integrated to evaluate single, short-term, and long-term exposure with BAX 855. These clinical trials included the following patients: previously treated adult, adolescent, and pediatric patients (PTPs) and previously untreated patients (PUPs). Immunogenicity, adverse events (AEs), and clinical laboratory parameters were assessed during prophylaxis, treatment of bleeding, perioperative management, and PK evaluations. Of 243 patients, the mean ±SD (range) age was 23.4 ±15.84 (0-61) years, there was 1 female; 74.9% of patients were White, 21.4% were Asian, and 2.5% were Black. Overall, 97 million IUs of BAX 855 were infused, resulting in a median (Q1; Q3) of 111 (73-196) exposure days (EDs) per patient, which ranged from 1 to 322 EDs. No patient developed inhibitory antibodies to FVIII (≥0.6BU) at any time. The 95% confidence intervals for developing inhibitory antibodies based on exposure are as follows: 0-0.19 for 191 PTPs with ≥50 EDs, 0-0.027 for 135 patients with ≥100 EDs, 0-0.37 for 98 patients with ≥150 EDs, and 0-0.68 for 52 patients with ≥200 EDs. At the time of the last blood sample analyzed, no patient had any antibodies to CHO proteins or persistent binding antibodies to FVIII, PEG-FVIII, or PEG. Binding antibodies were either pre-existing (28 patients) or transient (13 patients). No conclusion can be drawn as yet for 5 patients who developed binding antibodies shortly before or at the data cut-off for the analysis. The presence of binding antibodies could not be correlated to an altered PK or impaired efficacy. The only AE considered related to BAX 855 occurring in ≥1% of patients was headache; other related AEs (nausea; diarrhea, flushing, rash, and hypersensitivity) were observed in <1% of patients. No SAEs related to the use of BAX 855 were reported. One PUP discontinued due to a treatment-related AE: a mild, non-serious AE of hypersensitivity (a rash), which resolved. In total, 819 AEs were reported in 182/243 subjects administered ≥1 BAX 855 infusion. The overall rate of AEs/infusion was 2.7% (819 AEs/30,865 infusions), for non-serious AEs 2.5% (773 AEs/30,865), and for serious AEs 0.1% (46/30,865). No trends were observed in laboratory parameters or in vital signs. This safety update for BAX 855 confirms that the safety profile of BAX 855 is consistent with the safety profile of ADVATE. Overall, short- and long-term treatment with BAX 855 was safe and well tolerated in 243 pediatric, adolescent and adult subjects with severe hemophilia A from 3 completed and 4 ongoing studies. As experience with BAX 855 grows, this integrated safety update continues to confirm the safe use of BAX 855 for prophylaxis, the treatment of bleeding episodes, and perioperative management. Disclosures Engl: Shire, formerly Baxalta and Baxter: Employment, Equity Ownership. Patrone:Shire, formerly Baxalta and Baxter: Employment, Equity Ownership. Jacqueline:Baxalta US Inc., now part of Shire: Employment, Equity Ownership. Tangada:Baxalta US Inc., now part of Shire: Employment, Equity Ownership. Abbuehl:Shire, formerly Baxalta and Baxter: Employment, Equity Ownership.

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.

MODERN POSSIBILITIES OF SUBSTITUTION THERAPY AND HEMOPHILIA A PREVENTION IN CHILDREN

2021 ◽  
Vol 100 (2) ◽  
pp. 182-187
Author(s):  
P.A. Zharkov ◽  
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Hemophilia A ◽  
Safety Data ◽  
Residual Activity ◽  
Recombinant Factor Viii ◽  
Substitution Therapy ◽  
Life Effectiveness ◽  
Intravenous Injections ◽  
Prophylactic Use

Currently, the prophylactic use of factor VIII concentrate is the «gold standard» for treatment of an uncomplicated severe hemophilia A without inhibitors. However, there are a number of difficulties associated with frequent intravenous injections to maintain the activity of factor VIII above 1% in children and adolescents, which cannot but affect the adherence of patients to this type of treatment. The article discusses modern approaches to extend the half-life of recombinant factor VIII allowing to reduce the frequency of infusions and increase the residual activity of the deficient factor. On the example of efmoroctocog alpha, the first recombinant factor VIII concentrate registered in our country with a prolonged half-life, effectiveness and safety data of this class of drugs approved for use in children is presented.

Enhanced Half-Life Recombinant Factor VIII Concentrates for Hemophilia A: Final Results from Extension Studies

2021 ◽  
Author(s):  
Matteo Nicola Dario Di Minno ◽  
Alessandro Di Minno ◽  
Ilenia Calcaterra ◽  
Ernesto Cimino ◽  
Francesco Dell'Aquila ◽  
...  
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Hemophilia A ◽  
Recombinant Factor Viii ◽  
Factor Viii Concentrates

Quantitative Evaluation of Factor VIII in Factor VIII Products.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4012-4012
Author(s):  
Saulius Butenas ◽  
Behnaz Parhami-Seren ◽  
Matthew T. Gissel ◽  
Edward D. Gomperts ◽  
Kenneth G. Mann
Keyword(s):  
Factor Viii ◽  
Protein Content ◽  
Quantitative Evaluation ◽  
Hemophilia A ◽  
Specific Activity ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
Factor Viii Activity

Abstract Several factor VIII products, recombinant and natural, have been used for hemophilia A treatment worldwide. Typically, two activity-based assays (factor Xase and aPTT) are used for the assessment of factor VIII concentration in these products. Frequently, the results are dependent upon the assay and its modifications in different laboratories. In this study, we evaluated five pharmacologic factor VIII products (three lots of each) in three activity-based assays and in two immunoassays for the concentration and activity of factor VIII protein. Two factor VIII products were plasma-derived (Immunate and Hemofil M) and three were recombinant; two of these contained full-length factor VIII (Recombinate and Kogenate) and one was B-domainless (ReFacto). Albumin-free full-length recombinant factor VIII was used as a standard in all assays. In the factor Xase assay, all recombinant factor VIII products and Immunate at 1U/ml (indicated by manufacturer) showed activity similar to that of 0.7nM (1U/ml) standard, whereas activity of Hemofil M was 64–68% of the standard. In the aPTT assay both full-length recombinant products and Hemofil M displayed activity similar to the standard, whereas Immunate had increased (142% of standard) and ReFacto decreased (83% of standard) activity. In synthetic plasma, all three recombinant products had standard-like activity, whereas Hemofil M and Immunate were slightly more active than standard. The ELISA immunoassay revealed that the factor VIII protein content in Recombinate, Kogenate and Hemofil M corresponded to the units assigned by manufacturers (1.4–1.6x1012U/mol vs1.4x1012U/mol calculated for standard), whereas the specific activity of Immunate was 50% of that expected (0.7x1012U/mol). In contrast, the specific activity of ReFacto was almost 3-fold that of full-length factor VIII (4.0x1012U/mol). The data of this study indicate that: 1) factor VIII activity estimated in different assays gives dissimilar results; 2) the specific activity of factor VIII in various factor VIII products is different and, as a consequence, administration of an equal factor VIII activity in U/ml means the administration of different amounts of factor VIII protein.

Successful Treatment of Inhibitor Formation in Adult Congenital Hemophilia A with Rituximab.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4074-4074 ◽  
Author(s):  
Chirag J. Amin ◽  
Alice D. Ma
Keyword(s):  
Factor Viii ◽  
Knee Replacement ◽  
Immune Tolerance ◽  
Bolus Dose ◽  
Hemophilia A ◽  
High Titer ◽  
Tolerance Induction ◽  
Recombinant Factor Viii ◽  
Promising Alternative ◽  
Immune Tolerance Induction

Abstract Inhibitor development in congenital hemophiliacs can be clinically catastrophic. Immune tolerance induction therapy has previously been the standard of care in eradicating inhibitors; however due to a multitude of factors, this may not be applicable in certain patients. The role of Rituximab is receiving more attention in this subset of patients. In this abstract, we report that treatment with Rituximab led to successful eradication of high-titer inhibitors in 3 patients with mild to moderate hemophilia A who developed inhibitors after receiving intensive treatment with recombinant Factor VIII (FVIII). Patient Characteristics: Three patients, aged 50–70, with baseline FVIII levels of 2–9%, developed inhibitors after recombinant Factor VIII infusion. Patient A was treated with continuous infusion FVIII for a post-surgical hemarthrosis for approximately 7 days. Patient B received bolus dose FVIII for a GI bleed for at least 10 days, and Patient C received bolus dose FVIII for knee replacement for 10 days. Factor VIII inhibitors were detected in these patients after one month. None of these patients had been treated with immune tolerance previously or had known inhibitors. Each patient received Rituximab 375mg/m2 every week for 4 weeks total. During and after treatment, FVIII levels and Bethesda inhibitor titers (BU) were monitored. Results: All three patients had eradication of their inhibitors (Figure 1) and return of their FVIII levels to baseline by six months post-treatment. Notably, patient C’s inhibitor peak was 117 BUs, 7 months prior to Rituximab treatment. Patient C’s initial response to Rituximab has been previously reported at ASH in abstract form. We now report that 4 years later, this patient has had a recurrence of his inhibitor after monoclonal FVIII for a contralateral knee replacement but with a peak titer of only 2 (Table 1). Inhibitor Trends after Rituximab Treatment Inhibitor Trends after Rituximab Treatment Bethesda Inhibitor Titer (BU) per Month (*) after Receiving Rituximab 0* 1 3 6 36 48 51 NA=Not applicable as data has not matured yet Patient A (BU) 5 0.7 0 0 NA NA NA Patient B (BU) 17 7 2 0 NA NA NA Patient C (BU) 40 4 0 0 0 2 0.5 Conclusion: Inhibitors in patients with mild-moderate hemophilia differ from those with severe FVIII deficiency, behaving more like the autoantibodies seen in patients with spontaneous FVIII inhibitors. In support of this idea, we successfully treated high titer inhibitors which developed in 3 patients with baseline FVIII levels of 2–9%. All three patients had prompt resolution of their inhibitor titers during the course of therapy, with return of their baseline FVIII levels. Historically, patients with mild-moderate hemophilia treated at the Harold R. Roberts Comprehensive Hemophilia Center at the University of North Carolina were treated either with immune tolerance induction or by bypass agents alone, with inhibitor eradication taking months to years (data not shown). While performance of larger prospective trials would be ideal, the small number of patients with this condition limits the ability to perform these trials. Our findings, in combination with other case series from other institutions, reveal a promising alternative for prompt and reliable treatment in mild-moderate hemophiliacs with inhibitors.

Efficacy and Safety of Secondary Prophylactic Versus On-Demand Sucrose-Formulated Recombinant Factor VIII Treatment in Adults with Severe Hemophilia A: Results from a 13-Month Crossover Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 516-516 ◽  
Author(s):  
Peter Collins ◽  
Albert Faradji ◽  
Massimo Morfini ◽  
Monika Maas Enriquez ◽  
Eduard Gorina ◽  
...  
Keyword(s):  
Health Economics ◽  
Factor Viii ◽  
Crossover Study ◽  
Hemophilia A ◽  
Recombinant Factor Viii ◽  
Severe Hemophilia ◽  
Joint Function ◽  
On Demand ◽  
History Of ◽  
Male Patients

Abstract Many of the physical, psychosocial, and financial difficulties associated with severe hemophilia can be attributed to the effects of recurrent joint bleeds and chronic arthropathy. Regimens for clotting factor replacement treatment for hemophilia include prophylactic and on-demand therapy. A study in pediatric male patients with severe hemophilia A showed that prophylactic treatment with sucrose-formulated recombinant factor VIII (rFVIII-FS) resulted in prevention of joint damage and a decrease in the frequency of joint and other bleeds compared with on-demand therapy (Manco-Johnson MJ, et al. N Engl J Med.2007;357:535). A clinical trial was conducted in adult patients with severe hemophilia A and history of frequent bleeding to evaluate the effect of secondary rFVIII-FS prophylaxis on the number of joint bleeds after switching from on-demand rFVIII-FS therapy. Secondary study objectives were to compare these treatment strategies with regard to joint function, number of all bleeds, health-related quality of life, health economics, and safety. Male patients who were aged 30–45 years, had a negative inhibitor status, had a history of FVIII treatment (&gt;100 exposure days), and were using on-demand FVIII treatment before the study were eligible to participate in this prospective 13-month crossover study. During the first 6 months, all patients received on-demand rFVIII-FS treatment. Patients were then switched to prophylactic rFVIII-FS treatment (20–40 IU/kg 3 times per wk at a stable dose as determined by investigators based on the patient’s bleeding history) for the remaining 7 months, with the first month constituting a washout/stabilization run-in period. Patients were monitored throughout the 13 months for bleeds and health-economics parameters and were evaluated by the Gilbert score (joint function) and the Haemo-QoL questionnaire at baseline and at the end of the on-demand (at 6 mo) and prophylactic (at 13 mo) treatment periods. A total of 20 patients from 9 international sites participated in the study. Patients received a mean dose of 31 IU/kg/wk during the on-demand period, which increased to 86 IU/kg/wk during the prophylaxis period. Although 16/20 patients already had 1 to 4 target joints, mean (±SD) numbers of joint and total bleeds per patient significantly decreased during the prophylaxis period (1.5±2.1 and 1.9±3.3, respectively) compared with the on-demand period (18.5±11.6 and 23.7±13.3; P&lt;0.001 for both). Mean (±SD) total Gilbert scores indicated better joint function at the end of prophylaxis (19.8±11.7) vs on-demand (25.3±11.7; P&lt;0.001) treatment. During this short observation period, there was no statistically significant difference between treatments in the pharmacoeconomic variables assessed (days off work, general practitioner visits, and hospitalization days) or in the mean total Haemo-QoL score, although patients reported significantly fewer restrictions at work or school by the end of the prophylaxis period compared with the end of the on-demand period (P=0.016). There was a trend toward improved patient activity levels with prophylaxis. Similar numbers of patients reported adverse events (AEs) during on-demand (n=9, 45.0%) and prophylactic (n=10, 52.6%) treatment; AEs occurring in 2 patients (dysgeusia and headache) were considered treatment related. Serious AEs were reported by 1 patient during each treatment; neither serious AE was related to treatment. No de novo inhibitor development was observed during either treatment. In summary, prophylaxis with rFVIII-FS was well tolerated and reduced the frequency of joint and other bleeds compared with on-demand treatment in previously treated adults with severe hemophilia A and target joints.

Sign in / Sign up

Export Citation Format

Share Document