Abstract Introduction Narcolepsy type 1 (NT1) is a rare neurological disorder of central hypersomnolence, caused by the loss of orexin neurons. Symptoms include excessive daytime sleepiness (EDS), cataplexy, sleep-related symptoms (disrupted nighttime sleep DNS, hallucinations, sleep paralysis), and cognitive symptoms, which can be disruptive and persist despite treatments. This study examined clinical and humanistic burdens, and unmet need across the spectrum of disease severity among people with NT1 in the US. Methods A cross-sectional online survey of people with NT1, narcolepsy type 2, or idiopathic hypersomnia was conducted in the US. Participants were recruited from clinical sites, patient panels, and patient associations. Respondents completed information about demographics, symptoms, cognitive challenges, impacts, and disease severity assessments (Epworth Sleepiness Scale ESS, Narcolepsy Severity Scale for Clinical Trials NSS-CT). NT1 group findings are reported here. Results Overall, 247 participants (female: 74.9%) with NT1 and median (IQR) age of 40 (31-49) years were recruited. Key comorbidities included back pain (56.2%), anxiety (55.7%), and depression (53.1%). Most participants (211 87.2%) took narcolepsy medication in past 30 days (amphetamines (78 37.0%), modafinil (46 21.8%); 92.7% (229/247) participants reported EDS. Median (IQR) ESS total score was 16 (12-19), indicating severe EDS. Participants reported fatigue (92.9%) and taking daily naps (75.1%; median 2 naps/day); 184 (77.0%) had cognitive challenges and 63.0% (116/184) said these challenges were chronic. Overall, 207 (84.5%) experienced cataplexy (mean 5.61 episodes/week). Median (IQR) NSS-CT total score (23.5 16-31) indicated moderate to severe disease. According to NSS-CT, 68.9% had ≥1 hallucination episode/week, 67.4% were at least a little bothered by the hallucinations, and 55.3% reported having ≥1 sleep paralysis episode/week, with 39.5% being somewhat or very bothered by these episodes. DNS was experienced by 91.2% (217/238), with 34.5% reporting that it was very much disturbing. Conclusion Results highlight the substantial symptoms experienced by participants with NT1 despite current management, underscoring the unmet need for new therapeutic approaches. Novel treatments that target orexin deficiency have the potential to transform care beyond symptomatic management toward comprehensive disease control. Support (if any) Study was funded by Takeda Development Center Americas, Inc. Medical writing was funded by Takeda Pharmaceuticals U.S.A., Inc.
Jönsson et al. (Fri,) studied this question.