Brenda Riske

Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia

Recombinant adeno-associated virus (rAAV) is a promising gene delivery vector and has recently been used in patients with hemophilia. One limitation of AAV application is that most humans have experienced wild-type AAV serotype 2 exposure, which frequently generates neutralizing antibodies (NAbs) that may inhibit rAAV2 vector transduction. Employing alternative serotypes of rAAV vectors may circumvent this problem. We investigated the development of NAbs in early childhood by examining sera gathered prospectively from 62 children with hemophilia A, participating in a multi-institutional hemophilia clinical trial (the Joint Outcome Study). Clinical applications in hemophilia therapy have been suggested for serotypes AAV2, AAV5 and AAV8, therefore NAbs against these serotypes were serially assayed over a median follow-up of 4 years. NAbs prevalence increased during early childhood for all serotypes. NAbs against AAV2 (43.5%) were observed more frequently and at higher titers compared with both AAV5 (25.8%) and AAV8 (22.6%). NAbs against AAV5 or AAV8 were rarely observed in the absence of co-prevalent and higher titer AAV2 NAbs, suggesting that NAbs to AAV5 and AAV8 were detected following AAV2 exposure due to partial cross-reactivity of AAV2-directed NAbs. The results may guide rational design of clinical trials using alternative AAV serotypes and suggest that younger patients who are given AAV gene therapy will benefit from the lower prevalence of NAbs.

A Model for a Regional System of Care to Promote the Health and Well-Being of People with Rare Chronic Genetic Disorders

People with rare, inherited chronic health conditions, such as hemophilia, face added physical, social, emotional, and fiscal challenges beyond those that are common to more prevalent chronic conditions. In 1975, a partnership among clinicians, consumers, and government agencies created a nationwide regional health delivery system that increased access to clinical care, prevention, and research, thereby improving health outcomes for people with hemophilia in the United States. Today, more than 130 Comprehensive Hemophilia Diagnostic and Treatment Centers in 12 regions serve 70%-80% of the nations hemophilia patients. Health care leaders and advocates for other rare, expensive, chronic disorders may find that regionalization improves survival and reduces disability among affected populations. However, diverse and stable resources are needed to sustain such a model in our profit-oriented US health care arena.

Quality of life in haemophilia A: Hemophilia Utilization Group Study Va (HUGS‐Va)

Summary.  This study describes health‐related quality of life (HRQoL) of persons with haemophilia A in the United States (US) and determines associations between self‐reported joint pain, motion limitation and clinically evaluated joint range of motion (ROM), and between HRQoL and ROM. As part of a 2‐year cohort study, we collected baseline HRQoL using the SF‐12 (adults) and PedsQL (children), along with self‐ratings of joint pain and motion limitation, in persons with factor VIII deficiency recruited from six Haemophilia Treatment Centres (HTCs) in geographically diverse regions of the US. Clinically measured joint ROM measurements were collected from medical charts of a subset of participants. Adults (N = 156, mean age: 33.5 ± 12.6 years) had mean physical and mental component scores of 43.4 ± 10.7 and 50.9 ± 10.1, respectively. Children (N = 164, mean age: 9.7 ± 4.5 years) had mean total PedsQL, physical functioning, and psychosocial health scores of 85.9 ± 13.8, 89.5 ± 15.2, and 84.1 ± 15.3, respectively. Persons with more severe haemophilia and higher self‐reported joint pain and motion limitation had poorer scores, particularly in the physical aspects of HRQoL. In adults, significant correlations (P < 0.01) were found between ROM measures and both self‐reported measures. Except among those with severe disease, children and adults with haemophilia have HRQoL scores comparable with those of the healthy US population. The physical aspects of HRQoL in both adults and children with haemophilia A in the US decrease with increasing severity of illness. However, scores for mental aspects of HRQoL do not differ between severity groups. These findings are comparable with those from studies in European and Canadian haemophilia populations.

Burden of illness: direct and indirect costs among persons with hemophilia A in the United States.

Abstract Objective: To examine the direct and indirect costs of hemophilia care among persons with hemophilia A in the US. Methods: Observational data were obtained from HUGS-Va, a multi-center study from six federally supported hemophilia treatment centers (HTCs). Eligible individuals completed a standardized initial questionnaire and were followed regularly for 2 years to obtain information on work or school absenteeism, time spent arranging hemophilia care, and unpaid hemophilia-related support from caregivers. Data from 1-year healthcare utilization records and 2-year clotting factor dispensing records measured direct medical costs. Indirect costs were imputed using the human capital approach, which uses wages as a proxy measure of work time output. Results: A total of 222 patients with complete data were included in the analysis. Two-thirds had severe hemophilia and the mean age was 21.1 years. The use of prophylaxis in severe hemophilia patients is associated with statistically significant reduction in the numbers of emergency department (ED) visits and bleeding episodes compared with those who were treated episodically. From the societal perspective, mild hemophilia costs

Men with severe hemophilia in the United States: birth cohort analysis of a large national database

59,101 (median:

US Hemophilia Treatment Center population trends 1990-2010: patient diagnoses, demographics, health services utilization.

7519) annually per person,

Physical functioning in boys with hemophilia in the U.S.

84,363 (median:

Haemophilia Utilization Group Study - Part Va (HUGS Va): design, methods and baseline data

61,837) for moderate hemophilia,

High School Completion Rates Among Men with Hemophilia

201,471 (median:

Determinants of Safer Sexual Behavior in a Long-term HIV-seropositive Population The Multisite Hemophilia Behavior Intervention Evaluation Project (HBIEP

143,431) for severe hemophilia using episodic treatment, and