Health care costs and resource use of managing hemophilia A: A targeted literature review

BACKGROUND: Hemophilia A (HA) is a rare, inherited, serious bleeding disorder characterized by a deficiency of blood clotting factor VIII (FVIII). HA is associated with considerable economic burden. OBJECTIVE: To identify, review, and summarize published studies on the health care resource use and costs of managing HA in the United States using a targeted literature review. METHODS: A comprehensive and targeted literature search was conducted in Embase, MEDLINE, and Cochrane Database of Systematic Reviews covering the period 2010 to 2022. We supplemented the search by searching gray literature (relevant abstracts, posters, and presentations of relevant scientific conferences from the past 6 years [2016 to 2022], reference lists, the Institute for Clinical and Economic Review reports, and other sources). Eligibility criteria were developed based on the population, interventions, comparators, and outcomes framework. For comparability, costs were adjusted to 2021 US dollars. RESULTS: A total of 40 publications, including 17 full-text papers, 21 abstracts, and 2 Institute for Clinical and Economic Review reports, met eligibility criteria. Total annual health care costs per patient ranged from $213,874 to $869,940 and are mainly driven by the cost and intensity of prophylaxis with FVIII replacement concentrates, bypassing agents, and, most recently, emicizumab. Generally, we observed substantial heterogeneity in estimated treatment costs for HA, which varied depending on HA severity, treatment type and intensity, age, weight, and inhibitor status. Patients with inhibitors incurred much higher costs, but annual FVIII treatment costs are increasing over time among a subset of adult patients without inhibitors. Only 2 studies reported indirect costs; these were $13,220 and $27,978 annually among patients without and with inhibitors, respectively. Parents of children with HA spent $8,252 on non–mental health services and $258 on mental health services annually. CONCLUSIONS: The annual health care costs of managing HA are substantial and vary widely, depending on the study population definitions and intensity of prophylaxis. Total health care costs are dominated by the cost of prophylaxis. Indirect costs are also important. More robust studies in various settings, subpopulations, and assessing the impact of emerging therapies are required to fully elucidate the changing societal and economic impact, particularly regarding indirect costs and productivity loss for individuals living with HA.