OBJECTIVES: New therapies for Hereditary Angioedema (HAE), a rare, genetic disease, are currently in development. This comprehensive review sought to assess the design and analysis capabilities of currently available HAE economic models.

METHODS: We conducted a systematic literature review (SLR) (PROSPERO 42022351716) of comparative health economic models in HAE between January 1, 2007, and July 1, 2022. We included models described in manuscripts, conference proceedings, and health technology assessment (HTA) reports. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to evaluate study quality; we assessed quality of reporting using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines. We abstracted data on model design, characterization of attacks (location, severity, duration), pharmacotherapies, analyses, and outcomes reported.

RESULTS: Twenty-two models met inclusion criteria. Overall, HTA submissions had higher GRADE and CHEERS scores versus publications. Fourteen models evaluated on-demand therapy only; four evaluated long-term prophylaxis only, and four evaluated both. Markov modeling methodology was the most common (n=7), followed by decision tree modeling (n=5). Five long-term prophylaxis models had time-horizons long enough to sufficiently capture all relevant costs and outcomes associated with this lifetime chronic condition. Only five models included all important aspects of disease burden. Fifteen models included health-related quality of life, however only two included the impact of route of treatment administration on quality of life. Only five models included all costs relevant to patients, payers, and society.

CONCLUSIONS: In this first-known systematic review of HAE economic models, we found that few existing frameworks accounted for the holistic burden of HAE attacks from multiple perspectives. To enable a comprehensive analysis, future HAE models should include all factors relating to disease burden, health related quality of life, and costs relevant to patients, carers, payers, and society.