Abstract
Background: Istradefylline is a selective adenosine A2A receptor antagonist approved for Parkinson’s disease (PD) patients with wearing-off symptoms. The Japanese phase III trial showed that 20 mg of orally administrated istradefylline decreased the Off-time. However, istradefylline showed prominent effects in some patients and no benefits in others. We examined the differences in characteristics between responders and non-responders who received 8 weeks of 20 mg/day istradefylline. Methods: Thirty-one patients were enrolled (age, 65.4 [SD 10.4] years; disease duration, 10.4 [SD 6.1] years; daily levodopa dosage, 553.2 [SD 228.7] mg; frequency of levodopa consumption, 4.7 [SD 1.5] times; levodopa equivalent dose, 811.2 [SD 307.5] mg). Results: There were significant differences (p < 0.05) in sex (male/female: 5/16, 6/4), age (62.9 (SD 10.4), 70.6 (SD 8.0) years), age at onset (51.9 (SD 12.3), 61.5 (SD 10.5) years old), age at dyskinesia onset (57.9 (SD 8.8), 67.6 (SD 7.2), and Epworth sleepiness scale scores (4.5 (SD 2.7), 11.2 (SD 6.7), p < 0.01) for the responders and non-responders, respectively. There were no differences in disease duration, On-time, Off-time, Unified Parkinson’s disease Rating scale scores, daily levodopa dose, levodopa equivalent dose, cumulative levodopa dose, or coffee intake. Conclusions: Younger or female patients who are not excessively sleepy during daytime are better candidates for the istradefylline therapy.
Highlights
Istradefylline is a selective antagonist of the adenosine A2A receptor, and has been approved for use in Parkinson’s disease (PD) with regard to anti-parkinsonian effects in patients with wearing-off symptoms [1]
Patients with PD were recruited according to the following specifications: 1) patients were diagnosed on the basis of the UK PD Brain Bank criteria [3]; 2) patients were medicated with levodopa and experienced wearing off; 3) patients featured a rating between 0 and 4 on the modified Hoehn and Yahr (H&Y) scale during the on-phase; and 4) patients wanted to reduce their off-phase disability and received 20 mg/day of istradefylline once in the morning in A.Y.’s outpatient clinic at the Juntendo University Koshigaya hospital between October 2013 and October 2015
Participants were excluded based on the following criteria: 1) patients experienced Parkinsonism due to diseases other than PD; 2) patients were diagnosed with other serious diseases, malignant tumors, or adverse events caused by drugs
Summary
Istradefylline is a selective antagonist of the adenosine A2A receptor, and has been approved for use in PD with regard to anti-parkinsonian effects in patients with wearing-off symptoms [1]. A recent phase III trial demonstrated that the oral administration of istradefylline (20 mg) reduced off time in patients, while 40 mg of istradefylline improved part III of the Unified Parkinson’s disease Rating scale (UPDRS) during on-phase [2]. While istradefylline demonstrated prominent effects in a number of patients; others experienced little or no benefit. To elucidate the epidemiological differences between istradefylline responders and non-responders, a retrospective analysis was performed
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