0760 Tracking Compliance with Lower-Dose Titration of Twice-Nightly Oxybates in Narcolepsy and Idiopathic Hypersomnia

Abstract Introduction Oxybate salts are effective agents for narcolepsy type 1 (NT1), type 2 (NT2), and idiopathic hypersomnia (IH), but utilization remains low due to adverse events, as well as patient and/or prescriber apprehension. For twice-nightly oxybates (TN-OXB), the traditional titration schedule begins at 4.5 grams split into two even nightly doses (“4.5GSTD”). This study aims to characterize outcomes utilizing lower-dose titration schedules. Methods We conducted a manual chart review of patients initiated on TN-OXB from 2021–2025. Inclusion required an initial dose < 4.5GSTD. For each patient, we collected diagnosis (NT1/NT2/ IH), age, gender, and BMI. Follow-up visit documentation was analyzed for symptom improvement, reason(s) for discontinuation, and final stabilized dose among those who remained on therapy. Primary outcomes were discontinuation rate and tolerability with lower-dose titrations compared to those using historical standard-dose titrations. Results From 2021-2025, 61 patients initiated a TN-OXB titration < 4.5GSTD: 51 female (83.6%), 10 male (16.4%). There were 26 NT1 (42.6%), 22 NT2 (36.1%), and 13 IH (21.3%) patients. Nineteen (31%) were actively titrating at the time of this publication and were omitted from analysis. Of the remaining 42 patients, 31 (73.8%) continued TN-OXB, while 11 (26.2%) discontinued therapy. Among NT1 patients, 15 (75%) continued, 5 (25%) discontinued. Among NT2 patients, 10 (71.4%) continued, 4 (28.6%) discontinued. Among IH patients, 6 (75%) continued, 2 (25%) discontinued. Eleven (26.2%) patients’ therapies were optimized with a stable dose < 4.5GSTD. Conclusion The discontinuation rate (26.2%) in lower-dose TN-OXB titration is similar to published data (26.6%) in a recent large real-world clinical practice analysis with traditional titration schedules (Drakatos P. et al., Sleep 2017;35:80-84). Given the well-known patient and prescriber apprehension to oxybates due to concerns about CNS depression among other potential adverse events, there may still be considerable advantage in lower-dose TN-OXB titration, as this method may mitigate such fears and thus increase utilization of this standard-of-care therapy for central hypersomnias. Additionally, this method led to discovery of a stable dose < 4.5GSTD in 26.2% of patients, which likely would not have been discovered using a traditional titration schedule. Support (if any)