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Prophylactic infusion of factor replacement products results in a reduction in long-term morbidity and mortality in patients with severe hemophilia. However, intravenous access is commonly through central venous access devices, wh...
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Prophylactic infusion of factor replacement products results in a reduction in long-term morbidity and mortality in patients with severe hemophilia. However, intravenous access is commonly through central venous access devices, which may result in complications such as infections and thrombosis. Available clinical data on extended half-life (EHL) factor replacement products indicate the potential for a significant reduction in the need for frequent infusions, eg, once per week for factor (F)IX and twice per week for FVIII. With the current generation of factor replacement products, individualized pharmacokinetics (pK) direct optimal prophylactic dosing. The available data on the EHL factor replacement products also confirm similar individualized variability. Optimal dosing of these therapies relies on accurate assays, of which there is a variety, although performance characteristics vary with the specific product being tested. Herein, the data on clinical trials and laboratory assays are reviewed. (c) 2016 Elsevier Inc. All rights reserved.
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Introduction: This study proposes a method to predict individual pharmacokinetics of a future product by using the individual pharmacokinetic profile on the current product and the PopPK models of the current and future product.
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The use of enhanced half-life (EHL) FVIII has improved the quality of prophylaxis in haemophilia A, but with a benefit that may vary from one patient to another. We analysed the pharmacokinetic data obtained with efmoroctocog alfa...
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The use of enhanced half-life (EHL) FVIII has improved the quality of prophylaxis in haemophilia A, but with a benefit that may vary from one patient to another. We analysed the pharmacokinetic data obtained with efmoroctocog alfa (rFVIII-Fc) in 114 patients and, in 47 cases, compared them to those previously measured with non-EHL FVIII. The in vivo recovery (IVR) of rFVIII-Fc measured with one stage clotting assay (OSA) and chromogenic assay (CSA) was 2.2 and 2.8 IU/mL per IU/kg, respectively. The median half-life (T-1/2) of rFVIII-Fc was 14.5 hours whatever the FVIII:C assay used, but variable and correlated with preinfusion VWF:Ag levels (r = .76). Both IVR and T-1/2 were lower in patients under 12 years old (2.4 IU/mL per IU/kg and 11.1 hours, respectively; CSA). PK study of rFVIII-Fc vs non-EHL FVIII showed a T-1/2 ratio of 1.4 in favour of rFVIII-Fc, regardless of the patient's age. However the relative increase in T-1/2 with rFVIII-Fc was lower than 30% in one-third of patients evaluated, particularly when the previous FVIII administered was a BHK-derived product. This study therefore suggests that analysis of individual PK profile in response to a specific FVIII concentrate is potentially useful before a switch in haemophilia A patients.
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Introduction: Primary factor VIII (FVIII) prophylaxis is the optimal treatment in children with severe haemophilia A. They are expected to benefit from extended half-life (T-1/2) FVIII coverage by reduced infusion frequency while ...
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Introduction: Primary factor VIII (FVIII) prophylaxis is the optimal treatment in children with severe haemophilia A. They are expected to benefit from extended half-life (T-1/2) FVIII coverage by reduced infusion frequency while maintaining haemostatic efficacy. Aims: To determine immunogenicity, pharmacokinetics (PK), efficacy, safety and quality of life of prophylaxis with a polyethylene glycol (peg)-ylated FVIII (BAX 855) based on full-length recombinant FVIII (ADVATE) in paediatric previously treated patients (PTPs) with severe haemophilia A. Methods: PTPs <12 years without history of FVIII inhibitors received twice-weekly infusions of 50 +/- 10 IU kg(-1) BAX 855 for >= 50 exposure days. Prophylactic dose increases to 收起
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Background Real-life data on pharmacokinetics of factor (F) VIII/IX concentrates, especially extended half-life (EHL), concentrates in large cohorts of persons with hemophilia are currently lacking.
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Background In a real-world analysis (RWA) conducted in the United States (US), median international units (IUs) of extended half-life (EHL) recombinant coagulation factor VIII (rFVIII) dispensed were 10% to 45% greater than standa...
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Background In a real-world analysis (RWA) conducted in the United States (US), median international units (IUs) of extended half-life (EHL) recombinant coagulation factor VIII (rFVIII) dispensed were 10% to 45% greater than standard half-life (SHL) rFVIII. The mean IUs of each rFVIII dispensed quarterly were obtained from two databases (N = 776). Methods A probabilistic model in a 1-year time horizon was used in order to analyze the cost comparison of SHL and EHL rFVIII products in Spain. In this analysis, mean IUs were those of the RWA, and frequency of use and prices for each rFVIII were obtained from sales estimates based on Spanish sources (IQVIA; euro, 2019) Results Data showed an average annual savings per patient of euro11,227 for SHL rFVIII versus EHL rFVIII products, with a savings probability of 75.5%. The results were stable in the sensitivity analyses. Not switching treatment from SHL to EHL rFVIII resulted in greater savings per patient (euro53,078), with a savings probability of 99.9%. Considering the frequency of rFVIII dispensation in the US, annual savings per patient would increase to euro16,350 in Spain, with a savings probability of 79.9%. Conclusions According to this model, use of SHL rFVIII versus EHL rFVIII products could lead to savings for the Spanish National Health System.
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Abstract The use of enhanced half‐life (EHL) FVIII has improved the quality of prophylaxis in haemophilia A, but with a benefit that may vary from one patient to another. We analysed the pharmacokinetic data obtained with efmoroc...
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Abstract The use of enhanced half‐life (EHL) FVIII has improved the quality of prophylaxis in haemophilia A, but with a benefit that may vary from one patient to another. We analysed the pharmacokinetic data obtained with efmoroctocog alfa (rFVIII‐Fc) in 114 patients and, in 47 cases, compared them to those previously measured with non‐EHL FVIII. The in vivo recovery (IVR) of rFVIII‐Fc measured with one stage clotting assay (OSA) and chromogenic assay (CSA) was 2.2 and 2.8?IU/mL per IU/kg, respectively. The median half‐life (T 1/2 ) of rFVIII‐Fc was 14.5?hours whatever the FVIII:C assay used, but variable and correlated with preinfusion VWF:Ag levels ( r ?=?.76). Both IVR and T 1/2 were lower in patients under 12?years old (2.4?IU/mL per IU/kg and 11.1?hours, respectively; CSA). PK study of rFVIII‐Fc vs non‐EHL FVIII showed a T 1/2 ratio of 1.4 in favour of rFVIII‐Fc, regardless of the patient's age. However the relative increase in T 1/2 with rFVIII‐Fc was lower than 30% in one‐third of patients evaluated, particularly when the previous FVIII administered was a BHK‐derived product. This study therefore suggests that analysis of individual PK profile in response to a specific FVIII concentrate is potentially useful before a switch in haemophilia A patients.
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Haemophilia A and haemophilia B are congenital X-linked bleeding disorders caused by deficiency of coagulation factor VIII (FVIII) and IX (FIX), respectively. The preferred treatment option for patients with haemophilia is replace...
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Haemophilia A and haemophilia B are congenital X-linked bleeding disorders caused by deficiency of coagulation factor VIII (FVIII) and IX (FIX), respectively. The preferred treatment option for patients with haemophilia is replacement therapy. For patients with severe disease, prophylactic replacement of coagulation factor is the treatment of choice; this has been shown to reduce arthropathy significantly, reduce the frequency of bleeds and improve patients’ quality of life. Prophylaxis with standard recombinant factor requires regular intravenous infusion at least two (FIX) to three (FVIII) times a week. Recombinant FVIII and FIX products with an extended half-life are in development, or have been recently licensed. With reported mean half-life extensions of 1.5–1.8 times that of standard products for FVIII and 3–5 times that of standard products for FIX, these products have the potential to address many of the unmet needs of patients currently treated with standard factor concentrates. For example, they may encourage patients to switch from on-demand treatment to prophylaxis and improve the quality of life of patients receiving prophylaxis. Indeed, extended half-life products have the potential to reduce the burden of frequent intravenous injections, reducing the need for central venous lines in children, promote adherence, improve outcomes, potentially allow for more active lifestyles and, depending on the dosing regimen, increase factor trough levels. Members of the Zürich Haemophilia Forum convened for their 19th meeting to discuss the practicalities of incorporating new treatments into the management of people with haemophilia. This review of extended half-life products considers their introduction in haemophilia treatment, including the appropriate dose and schedule of infusions, laboratory monitoring, patient selection, safety considerations, and the economic aspects of care.
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Practical, safe, and effective hemostatic approach to orthopedic surgery using Extended Half‐Life factor IX in hemophilia B. By intraindividual comparison, we found a lower FIX consumption, number of infusions, and cost compared ...
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Practical, safe, and effective hemostatic approach to orthopedic surgery using Extended Half‐Life factor IX in hemophilia B. By intraindividual comparison, we found a lower FIX consumption, number of infusions, and cost compared to plasma‐derived FIX.
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