Jean-Louis Pépin, Philippe Lehert, Raoua Ben Messaoud, Marie Joyeux-Faure, Christian Caussé, Jerryll Asin, Ferran Barbé, Maria R Bonsignore, Winfried Randerath, Johan Verbraecken, Sonya Craig, Yves Dauvilliers
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引用次数: 0
摘要
背景：阻塞性睡眠呼吸暂停（OSA）是一种常见的慢性呼吸系统疾病，与嗜睡和生活质量下降相关的残疾负担很重。尽管使用持续气道正压疗法（CPAP）进行了一线治疗，但许多患者仍会出现白天过度嗜睡（EDS）的残留症状。本研究旨在比较欧洲和/或美国授权用于该适应症的药物（莫达非尼/阿莫达非尼、舒利眠和匹多莫德）治疗 OSA 的相对疗效和安全性：在这项系统综述和网络荟萃分析中，通过对 PubMed、Embase 和 ClinicalTrials.gov 数据库（截至 2024 年 6 月 12 日）的文献检索，确定了对 OSA 成年患者的授权药物的疗效和安全性进行比较的随机对照试验（RCT）。主要疗效终点是埃普沃思嗜睡量表（ESS）和牛津睡眠阻力（OSLER）/保持清醒测试（MWT）的综合 Z 值。研究还计算了生活质量（QoL）、总体和特定心血管安全性以及获益风险比。该研究已在 PROSPERO 注册：CRD42023434640：在确定的 4017 项研究中，共纳入了 20 项 RCT，涉及 4015 名患者。对主观（ESS）和客观（OSLER/MWT）疗效结果 Z 值的综合分析表明，索利安非托（150 毫克；效应大小 [ES] = 0.66 [95% CI: 0.36, 0.96]）、匹多莫司（20 毫克；ES = 0.66[95%CI：0.44，0.88])和莫达非尼（200 毫克；ES = 0.54：[95%CI：0.33，0.74])；400 毫克；ES = 0.54 [95% CI：0.42，0.65])的疗效有临床意义的改善。在总体安全性方面，P-评分依次为安慰剂、pitolisant、莫达非尼200毫克、莫达非尼400毫克和solriamfetol；在效益风险比方面，pitolisant、solriamfetol、莫达非尼400毫克和莫达非尼200毫克：皮托利生、索利安非托和莫达非尼在维持 OSA 患者清醒方面的疗效相当。与索利安非妥和莫达非尼相比，匹多莫德具有更好的安全性和效益风险比。总体和心血管安全风险比表明，匹多莫德可能是患有多种心血管并发症的OSA患者的最佳选择：资助：Bioprojet.
Comparative efficacy, safety and benefit/risk of alerting agents for excessive daytime sleepiness in patients with obstructive sleep apnoea: a network meta-analysis.
Background: Obstructive sleep apnoea (OSA) is a common chronic respiratory disease associated with a high burden of disabilities related to sleepiness and reduced quality of life. Despite first-line treatment with continuous positive airway pressure (CPAP) therapy, many patients experience residual excessive daytime sleepiness (EDS). The aim of this study is to compare the relative efficacy and safety of medications authorised for this indication in Europe and/or the United States (modafinil/armodafinil, solriamfetol, and pitolisant) for OSA.
Methods: In this systematic review and network meta-analysis, randomised controlled trials (RCTs) that compared the efficacy and safety of authorised medications for adult patients with OSA were identified by literature searches of PubMed, Embase and ClinicalTrials.gov databases (up to 12 June 2024). The primary efficacy endpoint was combined Epworth Sleepiness Scale (ESS) and Oxford Sleep Resistance (OSLER)/Maintenance of Wakefulness Test (MWT) Z-scores. Quality of life (QoL), overall and specific cardiovascular safety, and benefit-risk ratios were calculated. The study was registered with PROSPERO: CRD42023434640.
Findings: Of 4017 studies identified, a total of 20 RCTs involving 4015 patients were included. Analysis of combined subjective (ESS) and objective (OSLER/MWT) efficacy outcome Z-scores showed that solriamfetol (150 mg; effect size [ES] = 0.66 [95% CI: 0.36, 0.96]), pitolisant (20 mg; ES = 0.66 [95% CI: 0.44, 0.88]), and modafinil (200 mg; ES = 0.54: [95% CI: 0.33, 0.74]); 400 mg; ES = 0.54 [95% CI: 0.42, 0.65]) had a clinically meaningful improvement in efficacy. P-scores ranked placebo, then pitolisant, modafinil 200 mg, modafinil 400 mg and solriamfetol for overall safety; and pitolisant, then solriamfetol, modafinil 400 mg and modafinil 200 mg for benefit-risk ratio.
Interpretation: Pitolisant, solriamfetol and modafinil had comparable efficacy for maintaining wakefulness in patients with OSA. Pitolisant had a better safety profile and benefit-risk ratio compared with solriamfetol and modafinil. The overall and cardiovascular safety risk ratios suggest that pitolisant might be the best candidate for patients with OSA with multiple cardiovascular comorbidities.
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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