Efficacy of Pitolisant 20 mg in Reducing Excessive Daytime Sleepiness and Fatigue in Patients with Obstructive Sleep Apnoea Syndrome: An Individual Patient Data Meta-analysis.

BACKGROUND AND OBJECTIVE: Excessive daytime sleepiness (EDS) and fatigue are major complaints in patients with obstructive sleep apnoea (OSA) syndrome. Pitolisant is an orally active selective histamine H3 receptor (H3R) antagonist/inverse agonist, which enhances histaminergic transmissions in the brain and thereby elicits strong wake-promoting effects. This article assesses the efficacy and safety of pitolisant 20 mg in patients with OSA, based on existing randomised controlled studies.

METHODS: An individual patient data (IPD) meta-analytical two-level (study-patient) hierarchical model was used assuming a random treatment effect. The Epworth Sleepiness Scale (ESS) and Oxford Sleep Resistance (OSleR) tests were co-primary endpoints.

RESULTS: A total of 512 patients, including 384 treated with pitolisant and 128 with placebo, were included in the analysis. Compared with placebo, pitolisant reduced mean ESS by - 3.1 (95% CI [- 4.1; - 2.1]; p < 0.001) and improved OSleR by 1.18 (1.02; 1.35, p = 0.022); 30% more patients had reduced fatigue (risk ratio [RR] = 1.3, [1.11; 1.53]), p = 0.001) and 46% more patients had improved Clinical Global Impression (CGI) (RR = 1.46 [1.12; 1.89], p = 0.005). No significant differences in safety endpoints were found. These results proved homogeneous across studies and subgroups of the population.

CONCLUSION: The results provide evidence of a significant benefit of pitolisant in improving EDS and fatigue, irrespective of baseline conditions.