LAUSR

While increased costs and mortality in people with narcolepsy are well-established, the underlying drivers of these outcomes remain underexplored. This study aimed to identify and quantify the probable causes of elevated direct costs, indirect costs, and mortality in people with narcolepsy versus controls. We reviewed patient-reported consequences of narcolepsy, focusing on those impacting healthcare resource use, productivity, and mortality. Costs, mortality, and prevalence of each impact in the US general population were obtained from nationally representative data. Systematic and targeted literature reviews identified odds ratios for each impact in people with narcolepsy versus controls, selecting values from the most representative and rigorous studies. Few studies provided separate odds ratios for narcolepsy type 1 and type 2 compared with controls, and those that did generally reported no significant differences between the types. A model was developed to deterministically calculate average age-adjusted costs and mortality for an individual with narcolepsy compared with a control. Treatment-related costs were excluded. The annual incremental cost of narcolepsy was $18,735 (2024 US Dollars) per person. The largest contributor was productivity loss ($8,645/year), followed by healthcare costs associated with non-vehicular accidental injuries ($2,480/year), cardiovascular disease and events ($2,310/year), depression and anxiety ($2,110/year), headaches/migraines ($1,620/year), suicidal thinking and behavior ($1,050/year), and motor vehicle accidents ($520/year). Fatal cardiovascular events, non-vehicular accidental injuries, motor vehicle accidents, and suicide resulted in a 40% greater risk of mortality for people with narcolepsy compared with controls (average lifetime hazard ratio 1.4). This study is the first to quantify increased costs and excess mortality in people with narcolepsy based on their probable causes. Our model results align with annual costs and mortality hazard ratios reported in previous database studies, while providing deeper insight into the specific contributors to narcolepsy’s economic burden. Identifying the most costly and fatal aspects of narcolepsy is a critical step towards assessing the value of treatments that reduce these impacts. Understanding the cost of illness and mortality also helps inform policymakers about the severity and unmet needs of this underappreciated yet devastating disease. Funded by Takeda Pharmaceutical Company Limited.