Objective:
In the 3-year SPINART study, routine prophylaxis and on-demand treatment were compared in adults with severe hemophilia A. We report final SPINART efficacy and safety results after 3 study years.
Methods:
The open-label, randomized, controlled, parallel-group, multinational SPINART study enrolled males aged 12–50 years with severe hemophilia A who had ≥150 exposure days with any factor VIII (FVIII) product, no inhibitors, no prophylaxis for >12 consecutive months in the past 5 years, and 6–24 documented bleeding events or treatments in the previous 6 months. All patients were treated with Bayer’s sucrose-formulated recombinant FVIII (rFVIII-FS), either on demand or as prophylaxis (25 IU/kg 3 times weekly, with dose escalation by 5 IU/kg permitted once per year). The primary efficacy endpoint, bleeding frequency (number of all bleeding episodes at 1 year), has been previously reported. Endpoints reported here are total and annualized numbers of all bleeding episodes, joint bleeding episodes, spontaneous bleeding episodes, and trauma-related bleeding episodes. Between-group comparisons of bleeding frequency were made within the framework of a negative binomial regression model to account for different follow-up times of patients who discontinued prematurely, with stratification variables (presence of target joints at baseline, number of previous bleeding episodes at baseline) included in the model. Safety variables included adverse events (AEs), serious AEs, and inhibitor development.
Summary:
84 patients (42 prophylaxis, 42 on demand) comprised the intent-to-treat population. The total number of all bleeding episodes during the 3-year study was significantly lower with prophylaxis versus on demand (median, 2.0 vs 96.5, respectively; P<0.0001). Annualized number of all bleeding episodes (median [quartile 1; quartile 3], 0.7 [0; 1.6] vs 37.4 [24.1; 52.6]), total joint bleeding episodes (median, 1.0 vs 67.0), and joint bleeding episodes per year (median, 0.3 vs 27.3) were all lower with prophylaxis versus on demand. The numbers of spontaneous and trauma-related bleeding episodes were also lower with prophylaxis versus on demand. Observed AEs were consistent with the established rFVIII-FS safety profile. No patient developed inhibitors.
Conclusions:
Long-term prophylaxis with Bayer’s rFVIII-FS is efficacious in decreasing bleeding episodes, including joint bleeding episodes, in adults with severe hemophilia A. 75% of prophylaxis patients had <2 bleeding episodes per year during the 3-year study. No inhibitors were reported.
The purpose of this project is to determine if children with hemophilia have gross motor delays. Gross motor skills include, but are not limited to walking, running, jumping, climbing, crawling, balancing, kicking, catching and throwing activities. The large muscles of the body are responsible for performing these types of activities. Strength, balance and coordination are needed to demonstrate and improve these skills. Children with hemophilia may experience internal bleeding in their joints or muscles, which limits their activity. Some children with hemophilia may be restricted from active play or sports for fear of getting an injury that could cause internal bleeding. When activity is restricted, there can be decrease in strength, balance and endurance. If a child has gross motor delays, it puts him at risk for injury when playing with his peers. Physical Therapy evaluations in the Hemophilia Treatment Center help determine changes caused by bleeding episodes. There are specific motor skills children master as they grow, which represent strength, balance and coordination. The comprehensive clinic visits do not allow time to complete an intensive gross motor assessment. Physical Therapists use Manual Muscle Testing, MMT, to grade the strength of each muscle group. MMT strength testing is not appropriate for young children and does not represent strength during functional activities. To accurately determine children's muscle strengths, a standardized gross motor test should be used. The PT at the Comprehensive Care Center for Inherited Blood Disorders will conduct gross motor evaluations in conjunction with the annual visit. The scores will be evaluated to determine which patients have gross motor delays, so they can be referred for therapy services. The BOT 2 is the standardized gross motor test that will be used to determine gross motor levels. The gross motor skills that will be evaluated include bilateral coordination, balance, running speed and agility, upper limb coordination and strength. All patients with hemophilia between the ages of 4 and 12 years will be eligible to be evaluated in the upcoming year with additional PT testing with their annual visit. Patients may be referred to therapy or given a home exercise program depending on the deficits noted during the assessments. The goal is to improve our standard of care at the HTC, by adding gross motor screening for our patients to ensure appropriate referrals are made for therapy services.
Objective:
To describe the rates of falls, injurious falls, and activity restriction due to fear of falling in a population of patients with hemophilia.
Methods:
As part of a study on identifying fall risk in patients with hemophilia, subjects completed a self-administered questionnaire inquiring about fall history over the previous 12 months.
Summary:
75 patients with hemophilia between the ages of 18 and 85 completed the questionnaire. 59 (79%) of these patients had hemophilia A, and 16 (21%) had hemophilia B. 34 (45%) had severe disease, 17 (23%) had moderate disease, and 24 (32%) had mild disease.
25 (33%) of the subjects reported a fall within the last 12 months. The average and median ages of the subjects who fell were 46 and 45 respectively, while the average and median ages of the non-fallers were 41 and 39.5 respectively. Of the 25 patients who fell, 11 (44% of fallers or 15% of total sample) reported an injury caused by the fall. 12 patients (16%) reported restricting activity due to fear of falling. The majority of subjects who reported a fall or injurious fall had mild disease (55 %.), with an average age of 45 and median age of 46.5. The majority of subjects who restricted activity due to fear of falling had mild disease (50%), with most subjects who restricted activity reporting a fall in the previous 12 months (58%)
Conclusions:
Fall rates in hemophilia patients in this study (33%) are similar to or higher than the fall rates found in community dwelling adults 65 years and older (22-33%), although the subjects in this study were younger. Injurious fall rates found in the study (15%) are higher than non-fatal injurious fall rates described in adults age 65 and up (5-11.5%), and similar to those found in adults with arthritis age 45 and up (16.2%). Subjects in this study with mild disease were more likely to fall and to be injured. Activity restriction due to fear of falling (16%) was lower than that found in older adults in other populations (20-60%).
This study suggests that fall risk screening may be an important component of the comprehensive evaluation of patients with hemophilia, including those with mild disease. These results should be confirmed in a larger population of patients and across different treatment centres. Further research into optimal fall risk screening, in-depth assessment and treatment in this population is warranted.
Objective:
Having a family member with a chronic disease often increases the burden in the family with more hospital visits, treatment administration, and increased expenses. Management of hemophilia patients with inhibitors can be very complex and challenging. Health-related quality of life (HRQoL) has become a recent focus of research in hemophilia. Data on the HRQoL of congenital hemophilia patients with inhibitors and their caregivers is limited.
Methods:
We report a case study of a 36 year old male diagnosed as a neonate with hemophilia A, who, at age 6 months, developed a high titer inhibitor. His titer levels ranged from 99 BU/ml to in the thousands. Throughout a 30 year period, he experienced frequent bleeding episodes with several severe bleeds requiring extended hospitalization and intensive care management. He completed a majority of his schoolwork from a hospital bed and was unable to hold a steady job. He used factor VIII (FVIII) bypassing agents on demand to manage the bleeding episodes. As an adult, immune tolerance induction (ITI) failed with recombinant FVIII (rFVIII). QoL was poor for this husband and father of two children due to extremely limited mobility and inability to provide household income. He needed double knee replacement but insurance coverage for the surgery was denied due to the presence of the inhibitor. ITI therapy was switched to human plasma-derived FVIII with double viral inactivation (Koate-DVI) 10,000 units per day with successful tolerization in 8 months; his inhibitor was undetectable. He is currently on a prophylactic regimen of 3000 units twice a week, has not experienced any adverse events, and has had no major bleeds and only one minor bleed in 4 years.
Summary:
Successful immune tolerance induction (ITI) was achieved in a 32 year old adult male with hemophilia A with daily self-infusion of human FVIII therapy containing naturally occurring von Willebrand factor. This patient’s QoL has significantly improved since initiation of a home-based ITI protocol with Koate-DVI. He has been able to have double knee replacement surgery with major improvement in mobility and started his own successful national business.
Conclusions:
Advances in therapies continue to improve the longevity and quality of life of patients with hemophilia A. Increased or maintained HRQoL are essential goals in health care among patients with a chronic disease. This case study demonstrates the importance of well-disciplined ITI therapy with a human plasma FVIII product for hemophilia A patients with inhibitors.
Objective:
My Life, Our Future (MLOF) is a national project directed by a partnership formed to: 1) conduct wide-scale genetic testing of the U.S. hemophilia community, thereby increasing the rate of patient testing above the currently estimated 20% and allowing carrier detection; 2) establish a repository of associated samples and data to support scientific discovery and treatment advances including informing inhibitor risk and disease severity.
Methods:
A multi-sector partnership was formed to make hemophilia genotype analysis available to the U.S. community. The National Hemophilia Foundation (NHF) educates consumers and supports recruitment. The American Thrombosis and Hemostasis Network (ATHN) provides hemophilia treatment center (HTC) provider education, a secure infrastructure for data collection, and point of access for research proposals. HTCs enroll patients, obtain samples and provide clinical results to patients. Puget Sound Blood Center (PSBC) serves as the central genotyping laboratory and sample repository. Biogen Idec provides scientific collaboration and initiative support.
A pilot study involving 11 HTCs was successfully completed in 2013, and patients continue to be enrolled at those and additional sites. Genotyping is performed through an initial screen by Next Generation sequencing of extracted DNA using a molecular inversion probe-based capture strategy. FVIII and FIX mutations are confirmed in the CLIA-certified PSBC hemophilia genomics laboratory using a separate DNA sample. A clinical laboratory report is returned to the HTC and results transmitted into the ATHN Clinical Manager database accessible only to the patient’s HTC providers. For patients who give informed consent, coded data and samples are stored in a research repository, which can be linked to coded clinical data from the ATHNdataset for future research applications. NHF’s national and local chapter educational programs increased awareness and educated families about MLOF.
Summary:
As of June 13, 2014, 25 HTCs were enrolling patients and 865 patients were enrolled. Of those patients, 168 opted for clinical genotyping only and 697 also gave informed consent to have data and samples entered into the research repository. Mutation analysis has been completed in 707 patients, including 354, 151 and 202 with severe, moderate and mild haemophilia respectively. By comparison to available hemophilia A and B databases, 61 novel mutations have been identified in 68 patients. Lessons learned from the initial stages of the program’s rollout helped us to improve our approach to recruitment and education about the importance of genotyping and research in hemophilia.
Conclusions:
My Life, Our Future is a novel partnership to address unmet needs for hemophilia genotyping services and research. Expanding participation in the program will increase clinical genotyping for patients with hemophilia, increase knowledge of FVIII and FIX mutations present in the U.S. hemophilia population, and provide a robust research repository for future scientific discovery.
