Shiga University of Medical Science

Narcolepsy is a chronic disorder that requires lifelong management; however, few studies have evaluated disease burden of narcolepsy. We estimated the healthcare burden of narcolepsy in Japan using data from the Japan Medical Data Center health insurance claims database.

This was a retrospective analysis of clinical burden, healthcare resource utilization, and costs among incident narcolepsy cases and matched controls identified between January 1, 2014 and December 31, 2019.

Of the 1317 incident cases; 889 (with 1778 controls) were analyzed for healthcare burden, 626 (with 1252 controls) for clinical journey, and 439 (no controls) for treatment patterns. The most common baseline comorbidity was non-narcolepsy sleep disorder (41.6 % cases vs 3.0 % controls), including insomnia (28.5 % vs 2.6 %) and sleep apnea (10.8 % vs 0.3 %; both p < 0.001). The most common nonsleep disorder comorbidities were depression (35.0 % vs 2.6 %), anxiety (30.4 % vs 2.7 %), and headache/migraine (18.1 % vs 5.5 %; all p < 0.001). Compared to controls, narcolepsy cases had more prescription claims in the year following index date (82.8 % vs 9.5 %; p < 0.001), higher rates of outpatient (2291.8 vs 674.9 visits/100 person-years; p < 0.001) and inpatient claims (56.8 vs 5.1/100 person-years; p < 0.001), and longer hospital stays (mean 2.9 vs 0.5 days; p < 0.001). Similarly, median HCRU costs were higher in cases than controls (total annual healthcare costs, $2531 vs $266; community pharmacy claims, $826 vs $47 per person; and outpatient claim costs, $1053 vs $188 per person year).

Narcolepsy carries a substantial comorbidity burden, a high rate of medication prescribing, and high healthcare resource use in Japan.

Autophagy plays an important role in the physiology and pathology of the liver. Several negative autophagy regulators have been discovered, including epidermal growth factor receptor (EGFR), mediated by activation of the PI3K/Akt/mTOR signaling pathway. Disabled-1 (Dab1) is one of the mediating adaptor factors of PI3K/Akt/mTOR signaling pathways. We investigated the potential impact of Dab1 on autophagy-related markers (LC3B, LAMP2A, HSC70, and GRP78) in the developing liver by using a model of yotari mice and compared it with autophagy marker expression in human liver development. Mouse embryos were obtained at gestation days 13.5 and 15.5 (E13.5 and E15.5), and a total of 5 normal human conceptuses were obtained between gestation days 5 and 10. Histological sections were analyzed by immunohistochemistry. The highest expression of the early endosome-forming factor LC3B and the microautophagy factor LAMP2a was observed at the transition from embryonic to early fetal phase, whereas the expression of the chaperones HSC 70 and GRP78 was highest at embryonic phase. The expression patterns of three of these factors in mouse liver were different from those in human liver: the expression of LC3B was high at E13.5, that of HSC 70 at 15.5, whereas the expression of GRP78 did not change significantly. On the other hand, the expression pattern of LAMP2a was similar to that in human development and was higher at E15.5 than at E13.5. Moreover, knockout of Dab1 resulted in significantly lower expression of LC3B and LAMP2a in mouse embryo livers (at E13.5), indicating a possible role of Dab1 in regulating autophagy during embryonic development in the liver.

Estimation of prevalence and incidence of narcolepsy and idiopathic hypersomnia (IH) is challenging owing to symptomatic overlap, underdiagnosis, and misdiagnosis, and epidemiological data are lacking in Asian populations. We estimated the prevalence and incidence of narcolepsy and IH in Japan.

The Japan Medical Data Center (JMDC) database includes healthcare claims data for employed individuals ≤74 years of age. Narcolepsy and IH cases were defined by ≥2 diagnosis codes within 12 months, or a multiple sleep latency test with ≥1 diagnosis code within 12 months. Estimated point-prevalences of diagnosed narcolepsy and IH were calculated for December 31, 2019. Incidences of narcolepsy and IH were estimated for the period January 1, 2014 to December 31, 2019.

Of 7,075,869 individuals enrolled in the database on December 31, 2019, 6,110,751 (86.4 %) had ≥12 months' continuous enrollment and were eligible for inclusion in the prevalence population. Age-sex standardized overall prevalences of narcolepsy and IH were 37.5 (95 % confidence intervals 35.9-39.1) and 7.7 (7.0-8.4) per 100,000 persons, respectively. Prevalence for both conditions peaked at age 20-29 years and declined with increasing age. Age-sex standardized overall incidences of narcolepsy and IH were 5.1 (4.8-5.4) and 1.2 (1.0-1.5) per 100,000 person-years, respectively. Narcolepsy and IH incidences peaked in the 10-19 and 20-29 years age groups then declined with increasing age.

This claims-based study provides updated estimates for the prevalence and incidence of narcolepsy in Japan, and the first estimates for prevalence and incidence of IH in Japan.