Objectives:
Contemporary real-world data on units dispensed and expenditures associated with use of standard half-life (SHL) and extended half-life (EHL) factor VIII replacement products in U.S. patients with hemophilia A are limited. This exploratory analysis of real-world administrative data was conducted to determine units dispensed and factor replacement product-related direct expenditures associated with currently marketed recombinant SHL and EHL FVIII products, and to examine inter-product switches.
Methods:
De-identified claims data from the commercially available Truven Health MarketScan® Research US claims database were used to identify direct expenditures and number of international units (IUs) dispensed for all patients with a diagnosis code of ICD-9 286.0/ICD-10 D66 who used SHL (SHL group) and/or EHL (EHL group) during the study period from Aug 1, 2014 to Jan 31, 2017. Data on switching from an SHL to an EHL factor VIII replacement product were captured in patients with continuous pharmacy enrollment for whom claims data were available for at least 1 calendar quarter and up to 1 year before and after the index date of a product switch. Descriptive statistics were used to analyze results.
Summary:
Cross-sectional analysis.
The SHL group comprised 415 patients, among whom six distinct SHL FVIII products had been dispensed, and the EHL group included 91 patients, among whom two EHL FVIII products had been dispensed. The age distribution of the two groups was similar (p =0.57), although the proportion of patients under 18 years of age was somewhat higher in the SHL group than in the EHL group (46.9% vs 36.2%). The median FVIII product dispensation per calendar quarter was 46,409 IU (IQR, 12,760-87,670 IU) (SHL) versus 67,375 IU (IQR, 50,524-98,264 IU) (EHL). Median expenditures per calendar quarter were substantially higher for EHL ($135,519; IQR, $100,320-186,557) than for SHL ($61,152; IQR, $18,593-115,845).
Switching analysis.
Of the patients in the EHL group, 29 had switched from one of three SHL FVIII products to one of two EHL FVIII products during the study period. The total median IU dispensation per calendar quarter increased following the switch from 58,598 IU (pre-switch, SHL) to 68,036 IU (post-switch, EHL; 16% increase), as did the factor-related expenditure ($76,553, SHL, versus $141,101, EHL; 84% increase).
Conclusion:
Real-world data derived from a large claims database, unadjusted for treatment regimen or hemophilia severity, reveal marked differences in metric units and expenditures among hemophilia A patients to whom SHL and/or EHL products were dispensed. Switching from an SHL to an EHL FVIII replacement product was associated with a substantial increase in units dispensed and factor expenditures. Further analyses, incorporating essential clinical characteristics, should be explored.
Objective:
Through the Annual Global Survey (AGS), the World Federation of Hemophilia (WFH) has been collecting national aggregate data on people with bleeding disorders since 1999. Lack of diagnosis and treatment for women and girls with bleeding disorders remains a challenge in the bleeding disorder community. Highlighting gender data from the AGS can help bring awareness to the issues facing women and girls.
Methods:
The Report on the AGS 2015 includes demographic and treatment-related data from 111 countries, representing 91% of the world population. The AGS began collecting data on gender distribution in 2007. Gender data from 2007 to 2015 is summarized.
Summary:
The Report on the AGS 2015 demonstrates that 65,284 women were identified as having a bleeding disorder. The five types of hereditary bleeding disorders with the largest proportion of women are: platelet disorders (65%), von Willebrand (VWD) Fibrinogen (56%), FXI deficiency (55%), and FV deficiency (Figure 1). A gender breakdown for hemophilia A and B indicates that there are women who are affected by hemophilia (N=3,988 (3%), N=1,328 (5%) for hemophilia A and B, respectively) (Figure 1). The most common bleeding disorder for women and girls is VWD. From 2007 to 2015, the reported number of women with VWD increased by 17,220 (21,710 – year 2007, 38,930 – year 2015). This is a 79% increase in the number of women identified with VWD compared to a 65% increase in men identified with VWD during the same time period.
Conclusions:
AGS data recognizes the women and girls around the world who are affected by bleeding disorders. The WFH Annual Global Survey data is available to the bleeding disorder community as an advocacy tool.
Objective:
To provide genotyping and enrollment into the My Life, Our Future research repository for individuals with Hemophilia and potential carriers by offering a community based outreach program.
Methods:
Utilizing the ATHN dataset, potential participants who had not been previously genotyped were identified. In addition, a recruitment letter was prepared and sent to invitees of the local NHF Chapter Annual Dinner. Interested subjects were instructed to contact the genetic counselor, who discussed the project and scheduled them in 15 minute research timeslots. A hospital mobile unit, stocked with medical supplies and a centrifuge, was obtained to provide a site for registration, phlebotomy and processing of specimens. Staff for the event included the following: three staff to consent participants; four staff providing venipunctures, two staff to process specimens, two staff to assist with registration and a driver for the mobile unit. Funding was secured through NHF to support the genotyping day.
Summary:
Fifteen subjects, including 3 males and 12 females, scheduled appointments for the 4-hour recruitment time period. In addition, three subjects were added the day of the project and a waiting list was started for those wishing to enroll at a future event. In total, 17 subjects were enrolled from 9 families. In several cases, family members from different generations enrolled, including an at-risk carrier female, her mother and grandmother. Ages of participants ranged from 4-91. All participants chose to participate in the research repository. One participant’s specimen had to be destroyed due to a mislabelled MLOF ID (an add-on subject). It took approximately 10 hours to prepare for the event including 2 hours of planning related to the mobile unit (5 staff) and 8 hours to develop the recruitment letter, prepare the IRB amendment, mail letters, schedule participants, prepare consent packets, obtain MLOF ID numbers, and arrange phlebotomy kits (4 staff). It took 5 hours and 12 staff to successfully implement the program on the genotyping day. In comparison, we typically process on average two patients per 4 hour comprehensive clinics held two times per month, with 2 staff involved with other concurrent job assignments.
Conclusions:
The outreach program is an effective way to recruit individuals for genotyping and participation in the MLOF research repository. Participants were excited to participate and inquired about future events. The event provided a relaxed atmosphere with extended family members present, allowing for multi-generational and diverse recruitment. When considering a genotyping day versus scheduled clinic time, additional preparation time is needed to arrange logistics and avoid error, but the number of participants is significantly increased.
Objective:
People with hemophilia frequently experience joint bleeds, resulting in pain and functional impairment. The P-FiQ study formally evaluated patient-reported pain descriptions, responses to standardized patient-reported outcomes (PROs) related to pain, and pain management strategies.
Methods:
Participants completed a pain/hemophilia history and 5 PRO instruments. Pain was assessed via 3 PRO instruments: EQ-5D-5L, Brief Pain Inventory v2 Short Form (BPI), and Short Form-36 v2 (SF- 36v2), and these instruments were assessed for reliability, consistency, and correlation with factors including patient-reported characteristics.
Summary:
P-FiQ enrolled 381 adult males with mild-severe hemophilia and a history of pain and/or joint bleeding. Most (65%) self-reported having arthritis/bone/joint problems. Thirty-two percent of participants reported experiencing both acute and chronic pain, 35% chronic pain only, 20% acute pain only, and 15% no pain. Of those reporting acute pain, most described the sensation as “sharp” (77%) or “aching” (65%); for those reporting chronic pain, most described the pain as “aching” (80%) or “nagging” (50%). Ankles (37%) and knees (24%) were commonly reported as the most painful joints. Many participants with acute/chronic pain reported using acetaminophen (62%/55%) or nonsteroidal anti-inflammatory drugs (34%/49%) to treat their pain in the past 6 months. Some participants indicated having moderate/severe/extreme (28%/12%/2%) pain/discomfort “today” as measured by the EQ-5D-5L pain/discomfort domain. For BPI (scale 0-10, 10 is most severe pain), median pain severity scores were 6.0 for worst pain, 3.0 for average pain, 2.0 for current pain, and 1.0 for least pain. Median BPI pain interference scores indicated interference with general activity (3.0), mood (3.0), walking ability (3.0), normal work (3.0), and enjoyment of life (2.0). On SF-36, most participants (90%) reported experiencing bodily pain, and 75% indicated that pain interfered with normal work in the last 4 weeks. Assessments of pain on PROs were highly correlated with one another. The following formal PRO assessments were associated with self-reported pain: pain/discomfort domain of EQ-5D-5L, BPI worst pain, least pain, average pain, and current pain, and SF-36 bodily pain. Greater extent of lifetime routine infusions was also associated with EQ-5D-5L pain/discomfort and SF-36 bodily pain.
Conclusion:
Pain severity and interference in people with hemophilia were identified consistently across several PROs, and correlated with patient-reported pain. In the comprehensive care setting, greater use of formalized assessment tools over time would improve dialogue and pain assessment between healthcare professionals and patients, document and validate the presence and extent of pain, establish and monitor individual goals for pain management interventions, and encourage the exploration of various pain management strategies and the evaluation of their overall quality and effectiveness.
Dr. Tine Wyseure obtained her Master’s degree in Drug Discovery and Development, and earned her Ph.D. in Pharmaceutical Sciences at the University of Leuven, Belgium. Since 2015, she has been a research associate in the lab of Dr. Laurent Mosnier at The Scripps Research Institute in San Diego. Dr. Wyseure’s 2016 JGP research fellowship award project is focused on investigating the effects of impaired TAFI activation in hemophilia on the progression of hemophilic joint disease. The lack of active TAFI worsens joint bleeding and chronic inflammation and drives the striking development of fragile blood vessels in diseased joints. In search of the missing link, Dr. Wyseure has discovered a novel paradigm on how the formation of new blood vessels is controlled by TAFI and suggests that patients with hemophilia may lack this control switch, causing the formation of unstable and leaky blood vessels.
