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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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There have been numerous advances in the field of hemophilia management in the past decade, including long acting factor products, non-factor products, and potentially curative interventions such as gene therapy. Each of these int...
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There have been numerous advances in the field of hemophilia management in the past decade, including long acting factor products, non-factor products, and potentially curative interventions such as gene therapy. Each of these interventions introduces exciting treatment modalities to patients with both hemophilia A and B, however they also pose a daunting array of possible management options. Adverse reactions to novel agents are being reported as more patients are treated and long-term sustainability of interventions such as gene therapy is yet to be determined. The practicing hematologist should be aware of the intricacies involved in customizing care for their individual patients and be aware of the monitoring strategies for each interventional strategy to avoid adverse events. Upfront cost vs. long term benefit should be considered as choices of treatment strategies are made, especially in resource poor countries. The goal of the newer agents is to decrease annualized bleed rates and avoid debilitating arthropathy. This article looks at current treatment models for prophylaxis and management of inhibitors, reviews the recent advances in the field (with bioengineered factor products, non-factor products and gene therapy) and summarizes the incorporation of these new interventions in the treatment plan for patients with hemophilia.
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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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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 Zurich 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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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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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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摘要 :
The mainstay of treatment of inherited coagulation disorders is based on the infusion of the deficient clotting factor, when available. Significant advances have been made over the past two decades in the production and availabili...
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The mainstay of treatment of inherited coagulation disorders is based on the infusion of the deficient clotting factor, when available. Significant advances have been made over the past two decades in the production and availability of factor replacement products. In spite of such progression, several issue are still unsolved, the most important being the need for frequent factor concentrate infusions and the development of inhibitory alloantibodies. To overcome these important limitations, several newer hemostatic agents with an extended half-life are at an advanced stage of clinical development. After a brief overview of hemostasis, this narrative review summarizes the current knowledge on the most promising novel products for hemostasis. The current status of gene therapy for hemophilia, the only therapeutic option to definitively cure this inherited bleeding disorder, is also concisely discussed.
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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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Introduction Extended half-life factor products have reduced annualized bleeding rates in hemophilia patients. The impact of extended half-life versus conventional factor products on hemophilia caregiver burden has not been invest...
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Introduction Extended half-life factor products have reduced annualized bleeding rates in hemophilia patients. The impact of extended half-life versus conventional factor products on hemophilia caregiver burden has not been investigated. This study aimed to evaluate caregiver burden in extended half-life versus conventional factor products for hemophilia A and B. Methods This cross-sectional web-based study of caregivers of people with hemophilia A or B was recruited from a panel research company and by word of mouth. Participants completed the Hemophilia Caregiver Impact measure, the PedsQL Family Impact Module (PedsQL), and the Work Productivity and Activity Impairment Questionnaire (WPAI). We also collected demographic, insurance coverage, and medical information related to the hemophilia patient(s). Burden differences were assessed using linear regression and matched cohort analyses. Results The sample ( n ?=?448) included 49 people who were caring for people on extended half-life factor products. Worse caregiver burden was associated with more infusions per week and more bleeds in the past 6?months. Regression analyses suggested that caring for someone who is on a extended half-life factor product is associated with lower emotional impact ( β ?=???0.11, p ?收起
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