0699 Real-World Experience and Impact of Fatigue in Narcolepsy and Idiopathic Hypersomnia: Survey Results from the ASPIRE Study

Abstract Introduction Fatigue—characterized by exhaustion and low energy—is a common and disruptive symptom among people living with narcolepsy and idiopathic hypersomnia (IH). Patients distinguish fatigue from sleepiness, and fatigue often persists despite treatment for excessive daytime sleepiness. This study evaluated the association of fatigue with work productivity and health-related quality of life (HRQoL) among those diagnosed with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and IH. Methods The ASPIRE study was an online survey conducted among US adults who reported being diagnosed with NT1, NT2, or IH by a clinician (recruited via Rare Patient Voice, Hypersomnia Foundation, and Sleep Consortium). Participants completed the PROMIS-Fatigue Short-Form 6a (PROMIS-Fatigue), which measured fatigue severity over the past week (T-score range: 33.4-76.8; higher scores=more severe fatigue). Subgroups were defined as mild-to-severe fatigue (T-score ≥55) versus normal fatigue (T-score < 55). Work and activity impairment were measured using the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, which assessed absenteeism, presenteeism, and activity impairment over the past week. HRQoL was assessed using EQ-5D-5L (scored 0-1; higher scores=better HRQoL) and EQ-Visual Analogue Scale (EQ-VAS) (scored 0-100; higher scores=better HRQoL). Results The sample included 366 participants (NT1=116; NT2=127; IH=123) with mean age ~40y. Over 80% were female and 55% were employed. Approximately 60% of participants were treated with non-amphetamine wake-promoting agents. The mean PROMIS-Fatigue score was 65.74 (SD=7.52), with 91% reporting mild-to-severe fatigue. Participants with mild-to-severe fatigue reported greater activity impairment (66% vs 28%; p< 0.001) and work impairment (59% vs 21%; p< 0.001) vs those with normal fatigue. Mean HRQoL scores were lower among those with mild-to-severe fatigue vs those with normal fatigue (EQ-5D-5L: 0.61 vs 0.88 [p< 0.001]; EQ-VAS: 58 vs 78 [p< 0.001]). Findings were consistent across NT1, NT2, and IH subpopulations. Conclusion In this general sample of NT1, NT2, and IH participants, an overwhelming majority reported mild-to-severe fatigue. Fatigue was associated with substantial impairments in daily functioning, work productivity, and HRQoL. Results suggest fatigue is a common and burdensome symptom regardless of disease subtype. These findings underscore the burden of fatigue and highlight the unmet need for effective treatments that address this debilitating symptom. Support (if any) Alkermes, Inc.