Clinician Preferences for Oxybate Treatment for Narcolepsy: Survey and Discrete Choice Experiment.

INTRODUCTION: Immediate-release sodium oxybate (SXB) has been Food and Drug Administration (FDA)-approved to treat narcolepsy since 2002; in 2020, a mixed-salt oxybates formulation was also approved. Both are taken at bedtime with a second dose taken 2.5-4 h later. A third oxybate option, an investigational extended-release SXB, may soon be available. This study was undertaken to understand clinicians' preferences between these 3 different oxybate treatments. METHODS: Clinicians in active clinical practice for 3-35 years and experience treating patients with narcolepsy were recruited. A 30-min web-based survey quantified narcolepsy disease-state attitudes, treatment perceptions, and satisfaction with oxybates on 9-point scales. A discrete choice experiment (DCE) of 12 choice sets, with 2 hypothetical treatment profiles in each, was used to capture clinician preferences about overall oxybate therapy preference, impact on patient quality of life (QoL), and patient anxiety/stress. Attributes associated with current therapies and those expected to be available in the near future were included in the design. RESULTS: The clinicians surveyed (n = 100) indicated that narcolepsy has a negative impact on patient QoL (mean rating, 7.7) and rated impact on QoL and treatment efficacy as the most important aspects of a narcolepsy treatment (mean rating, 7.3-7.7). Clinicians with experience prescribing oxybates had moderately high satisfaction with SXB and mixed-salt oxybates efficacy (mean ratings, 6.5-6.9) and safety (mean ratings, 6.1-6.7) and lower satisfaction with nightly dosing frequency (mean rating, 5.9 and 6.3, respectively). In the DCE, dosing frequency was the most important attribute driving overall product choice, patient QoL, and reducing patient anxiety/stress (relative attribute importance, 46.1, 41.7, and 44.0, respectively), with once nightly preferred over twice nightly. CONCLUSION: Clinicians indicated a significantly higher preference for the once-at-bedtime dosing schedule versus twice nightly in selecting oxybate therapies overall and when aiming to improve patient QoL or reduce patient anxiety.

Current medications for narcolepsy include immediate-release sodium oxybate and mixed-salt oxybates. People taking these oxybates for narcolepsy take 1 dose at bedtime and must wake up 2.5­4 h later for the second dose. An investigational sodium oxybate, designed as a single bedtime dose, has been tentatively approved by the US Food and Drug Administration. This study used a 30-min web-based survey to learn what clinicians think about narcolepsy and narcolepsy medicines. A discrete choice experiment was used to identify which properties of current/future oxybate medicines are most important in a narcolepsy treatment. In this exercise, relevant properties of current/future oxybate medicines were mixed and matched to create hypothetical medicine profiles. Clinicians selected from these profiles which medication they preferred overall, which would improve patient quality of life, and which would reduce patient anxiety when thinking about taking the treatment. Clinicians were moderately satisfied with the effectiveness and safety of current narcolepsy medications. They strongly preferred oxybate treatments with fewer nightly doses and agreed that waking up for the second oxybate dose causes stress for patients. In the discrete choice experiment, the number of doses each night was the product characteristic that had the biggest impact on clinicians picking a medicine for narcolepsy. This was true for overall medicine choice, choosing a medicine that would improve patient quality of life, and choosing one that would reduce patient anxiety/stress. If granted marketing approval, extended-release sodium oxybate will be a once-at-bedtime option that may overcome challenges with current oxybate therapies.

Living with Narcolepsy: Current Management Strategies, Future Prospects, and Overlooked Real-Life Concerns.

Narcolepsy is a neurological disorder of the sleep-wake cycle characterized by excessive daytime sleepiness (EDS), cataplexy, nighttime sleep disturbances, and REM-sleep-related phenomena (sleep paralysis, hallucinations) that intrude into wakefulness. Dysfunction of the hypocretin/orexin system has been implicated as the underlying cause of narcolepsy with cataplexy. In most people with narcolepsy, symptom onset occurs between the ages of 10 and 35 years, but because the disorder is underrecognized and testing is complex, delays in diagnosis and treatment are common. Narcolepsy is treated with a combination of lifestyle modifications and medications that promote wakefulness and suppress cataplexy. Treatments are often effective in improving daytime functioning for individuals with narcolepsy, but side effects and/or lack of efficacy can result in suboptimal management of symptoms and, in many cases, significant residual impairment. Additionally, the psychosocial ramifications of narcolepsy are often neglected. Recently two new pharmacologic treatment options, solriamfetol and pitolisant, have been approved for adults, and the indication for sodium oxybate in narcolepsy has been expanded to include children. In recent years, there has been an uptick in patient-centered research, and promising new diagnostic and therapeutic options are in development. This paper summarizes current and prospective pharmacological therapies for treating both EDS and cataplexy, discusses concerns specific to children and reproductive-age women with narcolepsy, and reviews the negative impact of health-related stigma and efforts to address narcolepsy stigma.

Listening to the Patient Voice in Narcolepsy: Diagnostic Delay, Disease Burden, and Treatment Efficacy.

STUDY OBJECTIVES: Describe common symptoms, comorbidities, functional limitations, and treatment responsiveness among patients with narcolepsy. Investigate the effect of pediatric onset of narcolepsy symptoms on time to diagnosis of narcolepsy and presence of comorbid depression. METHODS: Cross-sectional survey of 1,699 people in the United States with self-reported diagnosis of narcolepsy. We utilized mixed-methods data analyses to report study findings. RESULTS: Most participants reported receiving a diagnosis of narcolepsy more than 1 y after symptom onset. We found that the strongest predictor of this delayed diagnosis was pediatric onset of symptoms (odds ratio = 2.4, p < 0.0005). Depression was the most common comorbidity but we detected no association with pediatric onset of narcolepsy symptoms. Overall, participants reported that fatigue and cognitive difficulties were their most burdensome symptoms in addition to sleepiness and cataplexy. The majority of participants reported residual daytime fatigue and/or sleepiness despite treatment. Most participants reported they could not perform at work or school as well as they would like because of narcolepsy symptoms. CONCLUSIONS: This study provides unique insight into the narcolepsy disease experience. The study quantifies the problem of diagnostic delay for narcolepsy patients in the United States and highlights that symptoms are more likely to be missed if they develop before 18 y of age. These results suggest that narcolepsy awareness efforts should be aimed at parents, pediatric health care providers, school professionals, and children/adolescents themselves. Disease burden is high because of problems with fatigue, cognition, and persistence of residual symptoms despite treatment.