OBJECTIVES: Patients with RD are differentially impacted in their day-to-day lives. This study aimed to explore work/activity impairment across six 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 (from 2020 for conference proceedings) and presented data on healthcare resource utilization or direct/indirect costs. Citations were assessed by two reviewers, with discrepancies reconciled by a third. For this sub-analysis, data for the impact on work/activity were single-extracted.

RESULTS: 1,238 citations were assessed, with 189 studies included overall; 39 reported data relating to the impact of RD on work/activity (HD:12, DEB:2, HAE:18, ATTR:4, SD:0, A1AT:3). Employment rate varied substantially across RD, highest in HAE (59%-69%) and A1AT (39%-55%) and lowest in DEB (26%), HD (15%-28%), and ATTR (6%-37%). HD has the most overall work impairment (48%-61%). However, higher employment rates mean A1AT incurs the greatest annual cost due to missed days (€4,395), with up to 22% absenteeism and up to 41% presenteeism reported. Similarly, higher employment rates mean HAE incurs the highest annual cost for lost productivity ($14,243) but the lowest impact on activity impairment (28%-34%; ATTR: 33%-56%, HD: 58%-79%).

CONCLUSIONS: Patients with RD face significant work productivity and social activity challenges. Substantial work/activity impairment and low employment rates were observed in HD, potentially linked to cognitive decline. Although ATTR has a later onset and more patients may be retired, considerable work impairment is observed for those who remain employed. In contrast, the lower activity impairment in HAE may reflect recent progress in improving treatment options. Lack of data suggests that productivity may be overlooked in some RD (e.g. SD).