Long-Term Efficacy and Safety of Pitolisant for Residual Sleepiness Due to OSA.

Background: In people with OSA, excessive daytime sleepiness is a prominent symptom and can persist despite adherence to CPAP, the first-line therapy for OSA. Pitolisant was effective in reducing daytime sleepiness in two 12-week randomized controlled trials (RCTs), one in patients adherent to CPAP (BF2.649 in Patients With OSA and Treated by CPAP But Still Complaining of EDS [HAROSA 1]) and the other in patients refusing or not tolerating CPAP (BF2.649 in Patients With OSA, Still Complaining of EDS and Refusing to be Treated by CPAP [HAROSA 2]).
Research Question: Does the efficacy and safety of pitolisant persist when these patients take it long-term?
Study Design and Methods: All adults included in the HAROSA 1 and HAROSA 2 RCTs (both pitolisant and placebo arms) were offered pitolisant (up to 20 mg/d) after completion of the short-term double-anonymized phase (ie, from week 13) in an open-label cohort study. The primary efficacy outcome was the change in Epworth Sleepiness Scale score between baseline and week 52. Safety outcomes were treatment-emergent adverse event(s) (TEAE[s]), serious TEAEs, and special interest TEAEs.
Results: Out of 512 adults included in the two RCTs, 376 completed the 1-year follow-up. The pooled mean difference in Epworth Sleepiness Scale score from baseline to 1 year for the intention-to-treat sample was -8.0 (95% CI, -8.3 to -7.5). The overall proportions of TEAEs, serious TEAEs, and TEAEs of special interest were 35.1%, 2.0%, and 11.1%, respectively, without any significant difference between patients in the initial pitolisant and placebo arms. No cardiovascular safety issues were reported.
Interpretation: Pitolisant is effective in reducing daytime sleepiness over 1 year in adults with OSA, with or without CPAP treatment. Taken for 1 year, it has a good safety profile (including cardiovascular).
Trial Registration: ClinicalTrials.gov; Nos.: NCT01071876 and NCT01072968; URL: www.
Clinicaltrials: gov.
Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: J.-L. P. reports administrative support and APC from Bioprojet during the conduct of the study; research grants from Agiradom, Air Liquide Foundation, Astra Zeneca, Bioprojet, Jazz Pharmaceuticals, Philips, Resmed, Sefam, and Vitalaire, outside the reported work; and honoraria or consultation fees from Agiradom, Somnomed, Bioprojet, ITAMAR, Jazz Pharmaceuticals, Philips, Resmed, and SEFAM, outside the reported work. C. C. is an employee of Bioprojet. Outside the reported work, J. V. has received institutional fees and educational grants from AirLiquide, AstraZen, Bekaert Deslee Academy, Bioprojet, Desitin, Ectosense, Epilog, Fisher & Paykel, Heinen & Löwenstein, Idorsia, Inspire, Jazz Pharmaceutics, Medidis, Mediq Tefa, OSG, Philips, ResMed, Sefam, SomnoMed, Total Care, UCB Pharma, Vivisol, and Westfalen Medical. Outside the reported work, R. T. reports research grants paid to his institution (Resmed, Inspire, BioProjet); personal lecture fees from Périmetres, Philips, Resmed, Jazz Pharmaceutical, and Bioprojet; and participation in advisory boards of Narval (Resmed), Bioprojet, and Idorsia. I. L. is an employee and shareholder of Bioprojet. Y. D. reports grants from Bioprojet, during the conduct of the study; and grants and/or consulting fees from UCB, JAZZ, Takeda, Theranexus, Harmony bioscience, Avadel, Paladin, and Idorsia, outside the submitted work. P. Lehert was a consultant statistician for Bioprojet during the conduct of the study; and is a consultant statistician for Merck, Sanofi, and Aguettant Pharma, outside the submitted work. None declared (V. A., J. H., and P. Lévy).
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)