Pitolisant long term effect in sleepy obstructive sleep apnea patients with CPAP

Introduction: Pitolisant is a histamine H3-receptor antagonist/inverse agonist waking agent reducing sleepiness in narcolepsy. Objectives: HAROSA2 1 year study evaluated Pitolisant 20mg/d (P) efficacy and safety on excessive daytime sleepiness (EDS) in moderate to severe obstructive sleep apnea patients (OSA) refusing CPAP. Methods: 2 periods were defined in HAROSA2: a 12 weeks double blind period (DB) comparing P vs placebo (pl) (n=268) and then was proposed a 40 weeks open label period (OL) with P (n=236). The primary criteria was the Epworth sleep scale (ESS) change and the main secondary critria were sleep latency OSleR test (OSL), Pichot fatigue score (PF) and safety. Results: After 1 year, in patients with P during DB, we observed an additional ESS reduction -1.6 ± 3.4, an increase of OSL and an improvement of PF -1.4 ± 5.9 during OL. In patients with pl during DB and P during PO, we observed an ESS reduction -5.2 ± 5.4, an increase of sleep latency and improvement of PF-2.9 ± 6.2. Most frequent side effects were headaches, insomnia, nausea, vertigo without cardiovascular impact observed. Conclusion: After 1 year, OSA patients without CPAP presenting EDS treated with Pitolisant during DB were improved during OL on ESS, OSL and PF: Pitolisant efficacy was maintained during 1 year. OSA Patients without CPAP presenting EDS with placebo during DB, then treated with Pitolisant (OL) were improved with a similar ESS reduction. Pitolisant showed a favourable benefit risk balance to manage EDSr in OSA patients refusing of not tolerating CPAP.