Long-term maintenance of efficacy and safety of pitolisant in the treatment of residual sleepiness in patients with Obstructive Sleep Apnoea

Abstract

<b>Rationale and objective:</b> In people with obstructive sleep apnoea (OSA) excessive daytime sleepiness (EDS) is a prominent symptom and can persist despite adherence to continuous positive airway pressure (CPAP). Pitolisant was effective in reducing EDS&nbsp;in 2 randomised controlled trials (RCTs), one in patients adherent to CPAP (HAROSA 1) and&nbsp;one in patients refusing or not tolerating CPAP (HAROSA 2). We asked whether the efficacy and safety of pitolisant persisted when taken long-term. <b>Methods:</b> All adults included in the HAROSA RCTs (both pitolisant and placebo arms) were proposed pitolisant (up to 20 mg/day) following the&nbsp;12 weeks&nbsp;double-blind phase, (open label period from week 13 to week 52). The primary efficacy outcome was the change in the Epworth Sleepiness Score (ESS) between baseline and week 52. Safety outcomes were treatment-emergent adverse event(s) (TEAE), serious TEAE and special interest TEAE. <b>Results:</b> Out of 512 adults included in the&nbsp;RCTs, 376 completed the 1-year follow-up. The pooled mean difference in ESS from baseline to one year for the Intention to Treat sample was -8.0 [-8.3, -7.5]. The overall proportions of TEAE, TESAE and TEAESI were 35.1%, 2.0% and 11.1%, respectively, without any significant difference between the initial pitolisant and placebo arms. No cardiovascular safety issues were reported. <b>Conclusion:</b> Pitolisant is effective in reducing daytime sleepiness over one year in adults with OSA, with or without CPAP treatment. Taken for one year it has a good safety profile (including cardiovascular).