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- Jean-Louis Pépin, Valérie Attali, Christian Caussé, Johan Verbraecken, Jan Hedner, Isabelle Lecomte, Renaud Tamisier, Patrick Lévy, Philippe Lehert, and Yves Dauvilliers.
- HP2 Laboratory, INSERM U1300, University Grenoble Alpes, Grenoble, France; EFCR (Cardiovascular and Respiratory Function) Laboratory, Grenoble Alpes University Hospital, Grenoble, France. Electronic address: JPepin@chu-grenoble.fr.
- Chest. 2024 Mar 1; 165 (3): 692703692-703.
BackgroundIn 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 QuestionDoes the efficacy and safety of pitolisant persist when these patients take it long-term?Study Design And MethodsAll 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.ResultsOut 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.InterpretationPitolisant 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 RegistrationClinicalTrials.gov; Nos.: NCT01071876 and NCT01072968; URL: www.Clinicaltrialsgov.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
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