isstradefylline治疗帕金森病的比较安全性：一项随机对照试验和现实世界研究的系统综述

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders Pub Date : 2025-01-01 DOI:10.1016/j.prdoa.2025.100307

Sagari Betté , Joyce Qian , Hannah Cummings , Hiroo Shimoda , Katsumi Shinoda , Ashley Thai , Sarah Batson , Gabrielle Redhead , Alexander Hodkinson , Daniel Truong

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引用次数: 0

摘要

istradefylline提供了一种新的机制（腺苷A2A受体拮抗剂）来治疗帕金森病（PD）的OFF发作。与其他辅助药物相比，它可能提供更好的耐受性，但缺乏相对安全性的数据。方法采用系统评价和贝叶斯网络荟萃分析（NMA），结合截至2024年1月10日的随机对照试验，评估PD辅助治疗的相对安全性。通过全球i2统计量和研究间异质性评估不一致性和异质性。根据相同的标准，总结了RWE确定的安全结果发生率。结果共纳入rct 100篇，RWE出版物55篇；nma共纳入76项随机对照试验。Istradefylline显示严重ae的发生率较低(优势比[OR] = 0.56；95% CrI: 0.32, 0.99)，治疗发生ae (0.43；0.25, 0.73)，治疗相关ae (0.33；0.19, 0.56)，幻觉(0.25；0.06, 0.97)， ae导致的退出(0.37；0.19, 0.68)对比金刚烷胺。iststradefylline显示运动障碍的几率较低(0.63；0.41, 0.99)和低血压(0.19；0.03, 0.82)与儿茶酚- o -甲基转移酶抑制剂（COMTi）相比，恶心的几率更低(0.58；0.33, 0.99)与多巴胺激动剂（DA）相比，低血压的几率更低(0.09；0.01, 0.52)对比单胺氧化酶- b抑制剂（MAO-Bi）。对2000年以来发表的随机对照试验的敏感性分析发现，与DA相比，司他替林减少了运动障碍和幻觉的几率。RWE是异质性的，但显示出司曲defylline的某些不良事件发生率较低，特别是运动障碍（与MAO-Bi相比）、嗜睡（与DA和COMTi相比）、周围水肿和幻觉（与金刚烷胺相比）和恶心（与所有比较物相比）。结论：rct和RWE表明，与其他PD辅助药物相比，istradefylline具有良好的安全性。

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Comparative safety of istradefylline in Parkinson’s disease: A systematic review of randomized controlled trials and real-world studies

Introduction

Istradefylline offers a novel mechanism (adenosine A_2A receptor antagonism) to treat OFF episodes in Parkinson’s disease (PD). It may potentially offer improved tolerability versus other adjuncts, but comparative safety data are lacking.

Methods

A systematic review and Bayesian network meta-analysis (NMA) incorporating RCTs of PD adjuncts until January 10, 2024, was conducted to estimate relative safety. Inconsistency was assessed and heterogeneity evaluated by global I²-statistic and between-study heterogeneity. Incidences of safety outcomes were summarized from RWE identified according to the same criteria.

Results

100 RCTs and 55 RWE publications were identified; 76 RCTs were included in NMAs. Istradefylline demonstrated lower odds of serious AEs (odds ratio [OR] = 0.56; 95 % CrI: 0.32, 0.99), treatment-emergent AEs (0.43; 0.25, 0.73), treatment-related AEs (0.33; 0.19, 0.56), hallucinations (0.25; 0.06, 0.97), and withdrawal due to AEs (0.37; 0.19, 0.68) versus amantadine. Istradefylline showed lower odds of dyskinesia (0.63; 0.41, 0.99) and hypotension (0.19; 0.03, 0.82) versus catechol-O-methyl transferase inhibitors (COMTi), lower odds of nausea (0.58; 0.33, 0.99) versus dopamine agonists (DA), and lower odds of hypotension (0.09; 0.01, 0.52) versus monoamine oxidase-B inhibitors (MAO-Bi). Sensitivity analysis of RCTs published since 2000 found a reduction in odds of dyskinesia and hallucinations for istradefylline versus DA. RWE were heterogeneous but demonstrated lower incidence of certain AEs with istradefylline, specifically dyskinesia (versus MAO-Bi), somnolence (versus DA and COMTi), peripheral edema and hallucinations (versus amantadine), and nausea (versus all comparators).