The Efficacy of Istradefylline for Treating Mild Wearing-Off in Parkinson Disease.

OBJECTIVES: The adenosine A2A antagonist istradefylline has been used to treat Parkinson disease (PD) with symptoms of wearing-off since 2013 in Japan. Previous randomized controlled trials of istradefylline compared with placebo included PD patients experiencing an average daily OFF time of more than 2 hours. The purpose of this study is to assess the efficacy of 20 mg/d istradefylline in PD subjects experiencing an average daily OFF time of 3 hours or less.

METHODS: Fifteen patients were enrolled into this retrospective study. They received 20 mg/d istradefylline for 12 weeks. Changes in the Unified Parkinson's Disease Rating Scale part III scores in the ON state (ON-UPDRS-III) scores and daily OFF time were assessed at baseline and after 4, 8, and 12 weeks of administration of istradefylline.

RESULTS: At baseline, all subjects had shorter daily OFF times, lower doses of L-DOPA and higher ON-UPDRS-III scores than those in previous randomized controlled trials. Twelve weeks of istradefylline significantly reduced ON-UPDRS-III scores (P < 0.001, Wilcoxon signed rank test). Eleven patients (73%) showed more than 50% reductions in ON-UPDRS-III scores. Improvement of ON-UPDRS-III was significantly correlated with baseline ON-UPDRS-III, and the mean ON-UPDRS-III score at end point was 12.1.

CONCLUSIONS: Our result suggests that 20 mg/d istradefylline significantly improved motor functions in PD patients with mild wearing-off.