Pitolisant efficacy in excessive daytime sleepiness for patients with obstructive sleep apnea

Abstract

Introduction: Pitolisant a Histamin H3-receptor inverse agonist waking agent for Excessive Daytime Sleepines (EDS) treatment in narcolepsy showed efficacy on EDS in Obstructive Sleep Apnea (OSA) patients with EDS treated respectively with and without Continuous Positive Airway Pressure (CPAP). Objective: Its efficacy and safety at 20mg/day was evaluated through an Individual patient data meta-analysis vs placebo.Methods: Epworth Sleep Scale (ESS) and Oxford Sleep Resistance (Osler) tests were co-primary endpoints tested at 0.025 significance and Fatigue (Pichot Scale) was secondary. Results: A significant mean ESS reduction of -3.06([95%CI -4.1,-2.02], Pl 0.001) was found with Pitolisant versus placebo and 81% more patients decreased final ESS to less than 10 (RR= 1.81 [95%CI 1.36, 2.39], pl 0.001). The Osler Final/Baseline was also 18% better (ratio=1.18[95%CI 1.02,1.35], P=0.022). A clinically meaningful EDS effect of Pitolisant measured by the aggregate Z-score on ESS and Osler was 0.71([0.46, 0.97], Pl 0.001). Finally, a significant mean Pichot Fatigue reduction of -1.23([-2.29,0.18], P=0.022) was found. These effects were shown invariant across various subgroups of the population (age,gender,work conditions). Finally these effects were not impacted as to whether or not CPAP was used. Side effect incidence was similar in both groups. Conclusions: These results confirm pitolisant efficacy on EDS and Fatigue symptoms in sleepy OSA patients versus placebo, evaluated by the ESS, Osler, EDS Z-score and Pichot Fatigue, irrespective of CPAP use. Bioprojet sponsored this analysis. CC is an employee of bioprojet pharma. JLP, YD, VA, were investigators, PL received honoraria from bioprojet.