Influence of istradefylline on non-motor symptoms of Parkinson's disease: A subanalysis of a 1-year observational study in Japan (J-FIRST)

Yasushi Shimo,Tetsuya Maeda,Shih-Wei Chiu,Takuhiro Yamaguchi,Kenichi Kashihara,Yoshio Tsuboi,Masahiro Nomoto,Nobutaka Hattori,Hirohisa Watanabe,Hidemoto Saiki

doi:10.1016/j.parkreldis.2021.09.015

Abstract

IntroductionThe non-motor symptoms (NMSs) of Parkinson's disease (PD) significantly impact the patient's health-related quality of life. This subanalysis of the J-FIRST study evaluated the effect of istradefylline, a selective adenosine A2A receptor antagonist, on NMSs in istradefylline-naïve Japanese patients with PD. MethodsPatients with PD and ≥1 NMS and ‘wearing-off’ with their current antiparkinsonian treatment were observed for up to 52 weeks. The effect of istradefylline on NMSs was measured in terms of changes in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 1 total, individual sub-items scores and the 8 item PD questionnaire (PDQ-8) estimated by the marginal structural model. ResultsOverall, 732 patients were istradefylline-naïve prior to the study, of whom 171 were treated with istradefylline for ≥8 weeks during the observation period (istradefylline-treated patients). At baseline, istradefylline-treated patients were more likely to have a dyskinesia (49.7% vs 40.8%) and received a significantly higher daily dose of levodopa (462.8 mg vs 413.0 mg) than those who did not receive istradefylline (n = 561). MDS-UPDRS Part 1 total score at the end of the 52-week observational period slightly increased in patients who received istradefylline and those who did not (0.49 ± 0.41 vs 0.07 ± 0.20; P = 0.36). There were no statistically significant differences between the two groups of patients in terms of changes in the MDS-UPDRS Part 1 total score or any sub-items, or in the PDQ-8 total score. ConclusionNMSs remained generally controlled in istradefylline-treated Japanese patients with PD who exhibited wearing-off with their current antiparkinsonian treatment. Istradefylline could be a feasible treatment option for patients with advanced PD, without worsening existing NMSs.

Highlights

The non-motor symptoms (NMSs) of Parkinson’s disease (PD) significantly impact the patient’s health-related quality of life
NMSs were generally well controlled by istradefylline in Japanese patients with PD who demonstrated wearing-off with their current antiparkinsonian treatment
Several studies have shown that istradefylline has positive effects on depression and anxiety in animal models and in pa tients with PD [10], our study showed no significant effects of istradefylline on these NMSs

Summary

Introduction

The non-motor symptoms (NMSs) of Parkinson’s disease (PD) significantly impact the patient’s health-related quality of life This subanalysis of the J-FIRST study evaluated the effect of istradefylline, a se lective adenosine A2A receptor antagonist, on NMSs in istradefylline-naïve Japanese patients with PD. The gold standard treatment for PD is dopamine replacement therapy using levodopa-containing preparations, because they provide control of motor symptoms, such as bradykinesia, rigidity and tremor, which occur as a consequence of loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). These treatments may achieve optimal outcomes when started in the early stages of the disease [3]. Relatively little is known about the management of NMSs, which are generally unre sponsive to the standard treatments used to control motor symptoms [4]

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