ArticleJournal of Parkinson's disease2021
Efficacy of Istradefylline, an Adenosine A2A Receptor Antagonist, as Adjunctive Therapy to Levodopa in Parkinson's Disease: A Pooled Analysis of 8 Phase 2b/3 Trials.
Article in Journal of Parkinson's disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Purinergic modulation in Parkinson's disease: the dual role of istradefylline in motor and cognitive outcomes.Purinergic signalling · 2026Review
- Lifestyle medicine in Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Current and emerging drugs for Parkinson's disease: mechanisms, clinical evidence, and future directions.Frontiers in pharmacology · 2026Review
- Treatment Options for Motor Fluctuations in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Impact of Adjunctive Istradefylline on Dyskinesia Onset in Patients with Parkinson's Disease Exhibiting Wearing-Off: An Open-Label Randomized Controlled Trial.Neurology and therapy · 2025Article
- Safety and Efficacy of Istradefylline in Parkinson's Disease Patients With and Without Preexisting Dyskinesia: Pooled Analysis of 8 Randomized Controlled Trials.Journal of movement disorders · 2025Article
- Moving to a non-dopaminergic approach for the treatment of OFF fluctuations in Parkinson's disease.Clinical parkinsonism & related disorders · 2025Review
- Adherence and persistence with istradefylline treatment in patients with Parkinson's disease in the United States.Frontiers in pharmacology · 2025Article
- Comparative safety of istradefylline in Parkinson's disease: A systematic review of randomized controlled trials and real-world studies.Clinical parkinsonism & related disorders · 2025Article
- Therapeutic exploration potential of adenosine receptor antagonists through pharmacophore ligand-based modelling and pharmacokinetics studies against Parkinson disease.In silico pharmacology · 2025Article
- Parkinson disease therapy: current strategies and future research priorities.Nature reviews. Neurology · 2024Review
- Istradefylline Improves Impaired Smooth Pursuit Eye Movements in Parkinson's Disease.Neurology and therapy · 2023Article
- Off-time Treatment Options for Parkinson's Disease.Neurology and therapy · 2023Review
- Real-world evidence on levodopa dose escalation in patients with Parkinson's disease treated with istradefylline.PloS one · 2023Article
- Istradefylline effects on tremor dominance (TD) and postural instability and gait difficulty (PIGD).Clinical parkinsonism & related disorders · 2023Article
- Newly Approved and Investigational Drugs for Motor Symptom Control in Parkinson's Disease.Drugs · 2022Review
- AMolecules (Basel, Switzerland) · 2022Article
- The Pharmacological Potential of Adenosine AMolecules (Basel, Switzerland) · 2022Review
- Amantadine delayed release/extended release capsules significantly reduce OFF time in Parkinson's disease.NPJ Parkinson's disease · 2022Article
- Istradefylline for OFF Episodes in Parkinson's Disease: A US Perspective of Common Clinical Scenarios.Degenerative neurological and neuromuscular disease · 2022Review
Corrections and comments
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Authors and funding
12 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIstradefylline is a selective adenosine A2A receptor antagonist for the treatment of patients with Parkinson's disease (PD) experiencing OFF episodes while on levodopa/decarboxylase inhibitor.
objectiveThis pooled analysis of eight randomized, placebo-controlled, double-blind phase 2b/3 studies evaluated the efficacy and safety of istradefylline.
methodsIstradefylline was evaluated in PD patients receiving levodopa with carbidopa/benserazide and experiencing motor fluctuations. Eight 12- or 16-week trials were conducted (n = 3,245); four of these studies were the basis for istradefylline's FDA approval. Change in OFF time as assessed in patient-completed 24-h PD diaries at Week 12 was the primary endpoint. All studies were designed with common methodology, thereby permitting pooling of data. Pooled analysis results from once-daily oral istradefylline (20 and 40 mg/day) and placebo were evaluated using a mixed-model repeated-measures approach including study as a factor.
resultsAmong 2,719 patients (placebo, n = 992; 20 mg/day, n = 848; 40 mg/day, n = 879), OFF hours/day were reduced at Week 12 at istradefylline dosages of 20 mg/day (least-squares mean difference [LSMD] from placebo in reduction from baseline [95%CI], -0.38 h [-0.61, -0.15]) and 40 mg/day (-0.45 h [-0.68, -0.22], p < 0.0001); ON time without troublesome dyskinesia (ON-WoTD) significantly increased. Similar results were found in the four-study pool (OFF hours/day, 20 mg/day, -0.75 h [-1.10, -0.40]; 40 mg/day, -0.82 h [-1.17, -0.47]). Istradefylline was generally well-tolerated; the average study completion rate among istradefylline-treated patients across all studies was 89.2%. Dyskinesia was the most frequent adverse event (placebo, 9.6%; 20 mg/day, 16.1%; 40 mg/day, 17.7%).
conclusionIn this pooled analysis, istradefylline significantly improved OFF time and ON-WoTD relative to placebo and was well-tolerated.
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