Exploring the Healthcare Resource Utilization (HCRU) Associated with Rare Diseases (RD) in the United States (US): A Systematic Literature Review (SLR) across Six Disease Areas

OBJECTIVES: HCRU differs across RD. This study investigated US HCRU in six different RD: Huntington's disease (HD), dystrophic epidermolysis bullosa (DEB), hereditary angioedema (HAE), transthyretin amyloidosis (ATTR), Stargardt disease (SD), and alpha-1 antitrypsin deficiency (A1AT).

METHODS: An SLR was conducted March 28, 2023 in Embase to identify the economic burden associated with each RD. Eligible studies were published from 2008 (2020 for conference proceedings) and presented data on HCRU or direct/indirect costs. Citations were assessed by two reviewers, with discrepancies reconciled by a third. For this sub-analysis, data associated with US HCRU were single-extracted.

RESULTS: 1,238 citations were assessed, with 189 studies included; 54 reported US data for HCRU (HD:17, DEB:2, HAE:10, ATTR:8, SD:1, A1AT:16). Annual healthcare costs were highest in HAE ($363,795), A1AT (up to $167,935, varying greatly according to treatment), and ATTR ($64,066). ATTR was associated with the longest mean inpatient stay and highest inpatient costs (20 days; $34,461/year), while HAE incurred the most frequent outpatient visits (up to 59 all-cause/year). Lower total costs were reported for dominant and recessive DEB (DDEB: $31,836; RDEB: $29,995) and HD ($27,120-$41,631), yet the proportion of patients requiring ≥1 annual inpatient stay was still notable in RDEB (33%) and HD (27%), and in DDEB all patients reported ≥1 annual outpatient visit. In addition, 36% of patients with HD require ≥1 annual emergency-room (ER) visit ($1,141/year), whereas HAE reported the lowest rate of ER visits (6%-9%).

CONCLUSIONS: Patients with RD incur substantial HCRU with varying cost drivers. For ATTR, inpatient visits were a key driver, for HAE outpatient costs were prominent, and for A1T1 treatment determined total cost. Although some RD had lower total costs, HD presented substantial ER burden, RDEB inpatient burden, and DDEB outpatient burden. Future treatments addressing unique drivers of HCRU in each RD will result in benefits for healthcare systems.