Safety Profile of Istradefylline in Parkinson’s Disease: A Meta-Analysis of Randomized Controlled Trials and Disproportionality Analysis Using FAERS
Author(s)
Beema T. Yoosuf, PhD Scholar, Muhammed Favas KT, PhD Scholar, Suhani Shri Sudarshankumar Jain, M Pharm, Dipika Bansal, MD.
Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, S.A.S Nagar, Mohali, India.
Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, S.A.S Nagar, Mohali, India.
OBJECTIVES: Istradefylline, a selective adenosine A2A receptor antagonist, is used as an adjunct therapy to levodopa to improve motor symptoms in Parkinson’s disease (PD) patients, particularly those experiencing wearing-off phenomena. This study integrates safety data on istradefylline for the treatment of PD from randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS).
METHODS: We performed a systematic search of PubMed, EMBASE, Ovid, MEDLINE, and ClinicalTrials.gov for RCTs on istradefylline safety in PD patients up to September 2024. A random-effects meta-analysis estimated the Peto odds ratio (OR) with 95% confidence intervals (CIs). FAERS data were analyzed through disproportionality measures, including the proportional reporting ratio (PRR) and reporting odds ratio (ROR), with signal refinement to primary suspect cases.
RESULTS: The safety meta-analysis, encompassing data from eight RCTs, reveals a significant association between istradefylline treatment and an increased risk of dyskinesia (odds ratio [OR] 1.77, 95% CI 1.32-2.36; p=0.0001), hallucinations (OR 2.08, 95% CI 1.11-3.90; p=0.022), and nausea (OR 1.50, 95% CI 1.06 - 2.11, p = 0.02), when compared with placebo. In the FAERS database, 2,597 patients were identified with adverse events (AEs) linked to valbenazine. Disproportionality analysis of istradefylline revealed 39 AEs strongly associated with its use, all of which were substantiated through signal refinement. The most commonly reported AEs were primarily associated with nervous system and psychiatric disorders.
CONCLUSIONS: This study highlights distinct AE patterns for istradefylline in trials versus real-world data, underscoring the importance of post-marketing surveillance to detect underreported AEs and validate new safety signals effectively.
METHODS: We performed a systematic search of PubMed, EMBASE, Ovid, MEDLINE, and ClinicalTrials.gov for RCTs on istradefylline safety in PD patients up to September 2024. A random-effects meta-analysis estimated the Peto odds ratio (OR) with 95% confidence intervals (CIs). FAERS data were analyzed through disproportionality measures, including the proportional reporting ratio (PRR) and reporting odds ratio (ROR), with signal refinement to primary suspect cases.
RESULTS: The safety meta-analysis, encompassing data from eight RCTs, reveals a significant association between istradefylline treatment and an increased risk of dyskinesia (odds ratio [OR] 1.77, 95% CI 1.32-2.36; p=0.0001), hallucinations (OR 2.08, 95% CI 1.11-3.90; p=0.022), and nausea (OR 1.50, 95% CI 1.06 - 2.11, p = 0.02), when compared with placebo. In the FAERS database, 2,597 patients were identified with adverse events (AEs) linked to valbenazine. Disproportionality analysis of istradefylline revealed 39 AEs strongly associated with its use, all of which were substantiated through signal refinement. The most commonly reported AEs were primarily associated with nervous system and psychiatric disorders.
CONCLUSIONS: This study highlights distinct AE patterns for istradefylline in trials versus real-world data, underscoring the importance of post-marketing surveillance to detect underreported AEs and validate new safety signals effectively.
Conference/Value in Health Info
2025-09, ISPOR Real-World Evidence Summit 2025, Tokyo, Japan
Value in Health Regional, Volume 49S (September 2025)
Code
RWD145
Topic Subcategory
Reproducibility & Replicability
Disease
SDC: Neurological Disorders