Pitolisant Plus CPAP Reduces Excessive Daytime Sleepiness in Patients With OSA

Pitolisant reduces residual excessive daytime sleepiness (EDS) among patients with obstructive sleep apnea (OSA) using continuous positive airway pressure (CPAP) therapy, according to the findings of a study published in the journal Sleep Medicine.

In previous studies, researchers have reported that pitolisant combined with CPAP reduced EDS among patients with OSA, however, these studies have lacked statistical power.

To more robustly evaluate the efficacy of pitolisant for reducing EDS, a team of researchers from University Hospitals Leuven in Belgium and Grenoble Alpes University in France conducted this individual patient data meta-analysis by searching publication databases through March 2024 for relevant randomized controlled trials (RCTs).

For the analysis, the researchers included data from the HAROSA I and III RCTs, which compared 20 mg or 40 mg pitolisant with placebo for 12 weeks.

The patients who received 20 mg pitolisant (n=183; mean age, 53.8 years; women, 18.6%), 40 mg pitolisant (n=120; mean age, 52.4 years; women, 25.0%), or placebo (n=120; mean age, 52.5 years; women, 17.5%) had a body mass index (BMI) of 32.7, 34.9, and 33.3 kg/m²; an apnea-hypopnea index (AHI) of 3.3, 4.8, and 4.4; and an Epworth Sleepiness Scale (ESS) score of 14.9, 14.2, and 14.0, respectively.

Both 20 (effect, 2.01; P =.007) and 40 (effect, 2.14; P =.005) mg pitolisant had greater treatment responses than placebo.

Compared with placebo, 20 mg pitolisant had significant effects on:

• ESS (standardized mean difference [SMD], 0.71; P =.001),
• Oxford Sleep Resistance Test (OSLER) time (SMD, 0.61; P =.001),
• EDS z-score (SMD, 0.89; P =.001),
• Clinical Global Impression (CGI) score (SMD, 0.60; P =.001),
• global z-score (SMD, 0.60; P =.001), and
• EuroQol Visual Analogue Scale (EQ-VAS) score (SMD, 0.52; P =.010).

Relative to placebo, the higher dose pitolisant intervention significantly affected outcomes for:

• ESS (SMD, 0.79; P =.001),
• OSLER time (SMD, 0.54; P =.021),
• EDS z-score (SMD, 1.29; P =.001),
• CGI score (SMD, 0.62; P =.001),
• global z-score (SMD, 0.89; P =.001),
• 5-level EQ-5D version (EQ-5D-5L) score (SMD, 0.54; P =.001), and
• Pichot fatigue score (SMD, 0.70; P =.001).

In a subgroup analysis, the effect of 20 mg pitolisant was mediated by age and AHI.

In the safety analysis, both the low (incidence rate ratio [IRR], 1.75; 95% CI, 1.25-2.44) and high (IRR, 2.40; 95% CI, 1.12-5.13) pitolisant doses associated with higher rates of treatment-emergent adverse events, whereas no differences were observed between pitolisant doses (IRR, 1.353; 95% CI, 0.597-3.065; P =.469). No group differences in the incidence in serious adverse events were observed.

This meta-analysis was limited by the overall paucity of data.

“Future research could provide additional insight on the long-term effects of pitolisant in treating residual EDS in patients with OSA who receive primary OSA therapy with CPAP. The relative effectiveness and benefit-risk ratio of pitolisant compared with other pharmacological treatment options in patients adhering to CPAP is unclear and additional research should be performed to assist the treatment decision-making of healthcare providers,” the researchers concluded.

Disclosure: This research was supported by Bioprojet-Pharma. Please see the original reference for a full list of disclosures