OBJECTIVES: The substantial economic burden associated with hereditary angioedema (HAE) has been well-documented; however, no systematic literature reviews (SLR) on the topic have been published to date. This study aimed to fill this gap by comprehensively synthesizing data on healthcare resource utilization (HRU) and direct medical costs associated with HAE.

METHODS: We conducted an SLR on economic outcomes, including HRU and costs, among patients using on-demand and prophylactic HAE therapies, in accordance with PRISMA guidelines. We searched multiple databases, including PubMed, Embase, and Google Scholar. Article inclusion was limited to English peer-reviewed and grey literature published between January 1, 2007 – July 1, 2022. Two independent reviewers assessed literature eligibility and abstracted data. We adjusted all costs for inflation to 2022 USD.

RESULTS: We identified 66 studies. The majority of studies were observational (64%) and peer-reviewed (58%), and the most common study location was the United States (42%). Among 53 peer-reviewed and congress proceedings, 79% assessed HRU and costs in HAE, revealing annual mean costs of up to $950,361 per patient. Medication accounted for the majority total direct costs (up to 85%, or $808,322), with prophylaxis treatment costing 2.42 times that of on-demand treatment only. For HRU, 90 – 92% of patients required at least one outpatient visit, up to 45% required at least one emergency department (ED) visit, and up to 21% required at least one inpatient stay annually. Regarding visit frequency, patients required an average of 2.7 – 3.7 outpatient visits, 1.94 ED visits, and 1.04 inpatient visits annually.

CONCLUSIONS: Despite the emergence of new HAE therapies during the past decade, individuals with HAE still experience high HRU and medical costs, indicating opportunities for improved disease management. The emergence of novel, non-parenteral HAE treatment options have the potential to mitigate HRU and costs, with benefits to patients and payers alike.