Introduction and Objectives:
Von Willebrand disease (VWD) is the most common bleeding disorder, affecting men and women equally. Despite this, awareness surrounding VWD is low. Outreach efforts often only target women, leaving many to assume VWD does not affect men. To begin changing this perception, the National Hemophilia Foundation (NHF) conducted a needs assessment to understand men’s awareness of VWD and experience getting a diagnosis for future programming.
Materials and Methods:
On behalf of NHF, The Harris Poll conducted a nationally representative online survey. From 2015 to 2016 1,002 adult men in the US were interviewed to learn about their health behaviors and awareness of VWD. A second online survey was conducted by NHF targeting men who were diagnosed with VWD to learn about their path to diagnosis and the impact of VWD on their lives. This survey was given to adult men in the US from 2016 to 2017 and 49 responses were included in the analysis.
Results:
The Harris Poll found that only 28% of men say they are aware of VWD and 68% are not sure of the symptoms. Medical providers (69%) are the main sources the men turned to for information about their health, followed by internet sources (40%). The second survey found an average of 8 years from first symptoms to final diagnosis, with almost 60% of respondents diagnosed at 18 years of age and older. When asked what motivated them to seek medical care, 45% cited a significant bleeding incident. Over half reported limitations to work, physical and social activity. Medical providers were one of the most common sources of information and support for men with VWD and the first place men went for information.
Conclusion:
More awareness of VWD is needed and outreach focused online and to medical providers. Diagnosed men need more education and support surrounding their disorder. NHF will continue to pursue outreach efforts and creation of resources for men with VWD.
Objective:
Physicians prescribing Factor VIII for haemophilia A patients are presented with an array of dose and dose frequency in the package insert making it difficult to precisely prescribe. To clarify the treatment outcome across products, a model of the published half-life was used to provide the expected % IU/dl +/- SD at 24, 48, 72, and 96 hours post dose at a normalized dose and at the high end of the recommended dosage (dose and freq.).
Methods:
Eleven rFVIII products recently marketed in the US were assessed using a model of the halflife +/- SD to calculate the expected %IU/dl +/- SD at 24, 48, 72, and 96 hrs post-dose. Terminal half-life data for adults was obtained from each published package insert (PI). The one-stage clotting assay data was used for all except Afstyla© (chromogenic assay only). Variance reported as coefficient of variation or confidence intervals was converted to standard deviation.
The first comparison was made using a standard dose of 50 IU/kg across all products. The second comparison used the maximum recommended dose and frequency for routine prophylaxis defined in the PI. Full data sets and curves of %IU/dl+/-SD under standard doses of 50 IU/kg and under maximum dose and frequency for routine prophylaxis have been generated.
Summary:
Graphing the single dose comparison (50 iu/kg) revealed 3 general clusters and one outlier at 24 hrs post dose. The first cluster had 4 products with a mean range of 21-25 %IU/dl at 24 hrs post dose. The second cluster had 5 products with a range of 30-32 %IU/dl at 24 hrs. The third cluster had 1 product (Eloctate©) with 43% IU/dl at 24 hrs. The outlier (Nuwiq©) showed exceptional variance compared to others and removed from discussion.
Expected %IU/dl was recalculated using the most frequent and highest dose recommended for individual products. Assessing the –SD value: 10 of 10 products achieved > 1% trough at 24 hrs; 8 of 10 at 48 hrs; 2 of 10 at 72 hrs; and 1 of 10 at 96 hrs. Note at 72hrs, only 2 of 10 products achieve minimal trough at –SD level when 4 of 10 claim q3day dosing.
Conclusions:
Initial dosing for routine prophylaxis relies on the mean half-life. The PK parameters are based on only 18 to 30 patients under well-controlled conditions. There is waste on both sides of the PK half-life distribution curve. Would it be reasonable to assure minimal breakthrough bleeds and less over-dosage by initiating treatment with a personal PK profile for each patient in order to identify the correct dose and frequency? This model could be used to find optimal dose and frequency with input from a personalized product half-life.
