Understanding Disease Burden Among Persons with Hemophilia Α without Inhibitors

Abstract Introduction Previous studies have reported significant disease burden in persons with hemophilia A (PwHA) who develop inhibitors to factor VIII. However, disease burden in PwHA without inhibitors (PwHA-WO) is not well understood across severities. The CHOICE Project was conducted in partnership between the US Centers for Disease Control and Prevention and the Hemophilia Federation of America to survey persons with bleeding disorders of varying severity, male and female, in the US. Participants in the CHOICE Project included both patients receiving care at federally funded hemophilia treatment centers (HTC) and those who do not receive care at HTCs. The objective of the study was to assess and characterize self-reported clinical outcomes, care, and quality of life (QoL) of PwHA-WO across all disease severities. Methods A retrospective analysis was conducted of data collected through the CHOICE Project, a cross-sectional survey, from April 2013 to July 2015. Adults (≥18 years) and caregivers of children with hemophilia A (HA) were recruited to take the 20-minute CHOICE survey, online or on paper, in English or Spanish. The overall response rate to survey questions was approximately 87%, but it varied by survey item, as participants could opt not to respond to certain questions. PwHA-WO were defined as HA persons that reported no current or past factor VIII inhibitors. In this analysis, self-reported demographics, bleed- and joint-related outcomes, treatment, and QoL among PwHA-WO were descriptively analyzed by self-reported disease severity. Results Of the total 429 PwHA surveyed, 328 (76%) reported no current or past inhibitors (PwHA-WO). The majority of PwHA-WO were adults (59%), males (80%), non-Hispanic (76%), or white (63%) and had commercial insurance (68%). More than a quarter reported depression or anxiety, while 13% and 23% reported diagnosis of human immunodeficiency virus and hepatitis C, respectively. Most patients reported seeking care from a hematologist (96%) or at an HTC (63%). Among PwHA-WO, a higher proportion reported having severe HA (severe, 63%; moderate, 15%; mild, 22%). Overall, 94% of PwHA-WO reported they had ever experienced a bleed (severe, 96%; moderate, 96%; mild, 88%; p=0.42), and more than 85% reported they had ever had a joint bleed (severe, 88%; moderate, 91%; mild, 72%; p=0.006). In the last 12 months, approximately 73% reported a joint bleed (severe, 76%; moderate, 78%; mild, 56%; p=0.025) and 65% reported a bleed in another location (severe, 70%; moderate, 62%; mild, 51%; p=0.17). About 15% and 22% of PwHA-WO reported a history of synovectomy (severe, 18%; moderate, 7%; mild, 11%; p=0.30) or joint replacement surgery (severe, 28%; moderate,19%; mild, 5%; p=0.015). Over 28% of PwHA-WO reported having joint problems such as pain, stiffness, and loss of motion "always" or "frequently" (severe, 32%; moderate, 29%; mild, 15%; p=0.23). About a quarter responded that these problems "always" or "frequently" limited their daily work/school, recreational, and/or self-care activities (severe, 29%; moderate, 24%; mild, 20%; p=0.46). On average, PwHA-WO reported 16 missed days from work, school, or usual activities due to their disease (severe, 12; moderate, 30; mild, 16; p=0.014). Nearly 66% of PwHA-WO reported using over-the-counter pain medication in the last 30 days (severe, 62%; moderate, 80%; mild, 67%; p=0.31) and over a third reported using prescription pain medication over the same period (severe, 44%; moderate, 30%; mild, 11%; p=0.01). Conclusions This study suggests that considerable clinical, emotional, and day-to-day disease burden exists in PwHA-WO, even among those with mild and moderate severity. Although joint bleed-related outcomes varied by severity, patients with moderate HA reported joint-related outcomes comparable to those with severe HA. However, limitation of daily activities did not differ by severity. PwHA-WO with mild, moderate and severe HA reported limitation in physical activities, which can impair their QoL. Better understanding of disease burden by severity among PwHA-WO will help in planning future interventions to address these burdens and improve health outcomes. Disclosures Owens: Divitius LLC: Employment; Genentech Inc.: Consultancy; HFA: Consultancy. Cyhaniuk:Independent Contractor: Consultancy; HFA: Employment; AC Analytical Solutions, LLC: Employment. Patel:Genentech Inc: Employment. Raimundo:Genentech Inc: Employment, Other: Ownership interests PLC. Chan:Hemophilia Federation of America: Employment. Ko:Genentech Inc: Employment; F. Hoffmann-La Roche Ltd: Other: Ownership interests non-PLC.