biostudies-literatureUnknown12Bette S<h4>Introduction</h4>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.<h4>Methods</h4>A systematic review and Bayesian network <i>meta</i>-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.<h4>Results</h4>100 RCTs and 55 RWE publications were identified; 76 RCTs were included in NMAs. Istradefylline demonstrated loClinical parkinsonism & related disorders100307https://www.ebi.ac.uk/biostudies/studies/S-EPMC11904592biostudies-literatureComparative safety of istradefylline in Parkinson's disease: A systematic review of randomized controlled trials and real-world studies.PMC11904592Qian JThai ABatson SShinoda KBette SShimoda HCummings HTruong DRedhead GHodkinson AfalseComparative safety of istradefylline in Parkinson's disease: A systematic review of randomized controlled trials and real-world studies.<h4>Introduction</h4>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.<h4>Methods</h4>A systematic review and Bayesian network <i>meta</i>-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.<h4>Results</h4>100 RCTs and 55 RWE publications were identified; 76 RCTs were included in NMAs. Istradefylline demonstrated lo2025-01-01T00:00:00Z20252025-04-26T05:46:59.88Z2025-04-06T11:40:41.695ZS-EPMC119045924008434610.1016/j.prdoa.2025.100307