Singh, Gajinder Pal

Abstract Introduction Narcolepsy is a chronic sleep disorder with multiple comorbid conditions. Sodium oxybate (SXB) is strongly recommended for treatment of narcolepsy. This study used aggregate electronic health record (EHR) data to characterize demographic characteristics and comorbidities of patients with narcolepsy treated with or without SXB. Methods An EHR-based search identified first-time Mayo Clinic patients between 1975–2020. Patients had ≥1 narcolepsy-specific ICD-9/-10 code and ≥1 diagnostic mention of narcolepsy in clinical notes (natural-language-processing algorithm). Patients with narcolepsy treated with SXB were age/sex matched with a cohort without SXB treatment. Common comorbidities were identified using ICD-9/-10 codes and compared between cohorts (odds ratio [OR]). Results Of 4387 patients identified, 8% received SXB treatment (n=351; mean [IQR] age at first diagnosis code observed at Mayo Clinic, 32 [23.2-46.1] y; 65.5% female; 92.3% white); 4036 patients had no SXB treatment (mean [IQR] age at first diagnosis code observed at Mayo Clinic, 44.8 [29.8-59.0] y; 58.0% female; 88.9% white). The 10 most commonly reported comorbidities (overall population) were insomnia (46.6%), fatigue (46.3%), depression (42.2%), hypertension (36.2%), hyperlipidemia (34.2%), obstructive sleep apnea (32.3%), diabetes mellitus (31.3%), arrhythmia (27.3%), idiopathic hypersomnia (IH; 26.8%), and coronary artery disease (17.6%). A cohort of 351 patients without SXB were age/sex matched to patients with SXB for comparison of comorbidities. In the unadjusted analysis, P values were significant for differences between cohorts (OR [95% CI] SXB vs no SXB) for fatigue (0.72 [0.54-0.97]; P< 0.05; adjusted P>0.9) and IH (0.60 [0.43-0.84]; P< 0.01; adjusted P=0.29). After P value adjustment (Bonferroni correction), there were no significant differences between these cohorts in ORs for any comorbidity. The matched cohorts, which were younger than the overall population, had numerically lower rates of these diagnoses vs the overall population, except fatigue and IH in patients without SXB and depression in patients with SXB. Conclusion Among age-/gender-matched cohorts of patients with/ without SXB, there were no significant differences in comorbidities. Prevalence of comorbid IH/narcolepsy diagnoses highlight the diagnostic challenge in differentiating IH from narcolepsy type 2. SXB is highly effective but used by < 1:10 patients with narcolepsy in the Mayo Clinic health system. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Sodium oxybate (SXB) is strongly recommended for treatment of narcolepsy. Patients treated with available immediate-release oxybates are required to awaken for a second dose 2.5–4 hours after the bedtime dose to cover a full night of sleep. This study characterized SXB treatment patterns and discontinuation in narcolepsy patients. Methods Mayo Clinic patients from 1975–2020 were identified using an electronic health record–based search. Patients with ≥1 narcolepsy-specific ICD-9/-10 code and ≥1 diagnostic mention of narcolepsy in clinical notes (identified using a natural-language-processing [NLP] algorithm) were included. NLP was used to identify SXB non-use events with manual chart reviews performed to characterize reasons for discontinuation, switching, or missing the second dose and effects of missing the second dose. Results Of the patients with narcolepsy prescribed SXB (n=351; mean age at first diagnosis code observed at Mayo Clinic, 32 y [IQR: 23.2–46.1]; 65.5% female; 92.3% white), 113 (32.2%) had clinical notes indicating discontinuation of SXB, with 71 (20.2%) including reasons for discontinuation. The most common reasons for discontinuation (n≥5) included lack of efficacy (n=11), side effects (n=10), gastrointestinal side effects (n=10), neurological side effects (n=9), psychiatric side effects (n=8), lack of access (insurance/cost, n=10), and resolution/absence of cataplexy (n=5). Mentions of switching from SXB to other drugs (n=12 patients) included switching to stimulants (mixed amphetamine salts, n=3; dextroamphetamine, n=2; methylphenidate, n=1), sedative hypnotics (zolpidem, n=2), antidepressants (mirtazapine, n=1), and wake-promoting agents (solriamfetol, n=1). Of the 38 patients (10.8%) with mentions of missing the second nightly SXB dose, reasons were recorded for 24 (63.2%), including inability to wake up (n=14), forgetting the second dose (n=3), and having to wake up early the following day (n=3). Consequences of missing the second dose were recorded for a small subset (increased cataplexy, n=4; lower daytime alertness, n=3; awakens earlier, n=1; tiredness, n=1). Conclusion Limited data are available regarding real-world use of SXB. This novel study used a combination of NLP algorithm and manual chart review to identify difficulties patients have with the second, middle-of-the night immediate-release oxybate dose and patient-experienced consequences of not adhering to the prescribed dosing regimen. Support (if any) Avadel Pharmaceuticals