Objective: To examine the effects of istradefylline on motor and non-motor symptoms in Parkinson’s disease (PD) patients with wearing-off phenomena.

Background: Previous results [1,2] of the ISTRA ADJUST PD study showed that in PD patients with wearing-off, istradefylline, an adenosine A_2A receptor antagonist, significantly improved Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part I, III, and IV scores. In this study, we examined the effects of istradefylline on MDS-UPDRS subitems and Parkinson’s Disease Questionnaire-39 (PDQ-39) subitems.

Method: The 37-week, multicenter, randomized, open-label, parallel-group, controlled, ISTRA ADJUST PD study was conducted as described previously [1,2]. Patients were randomized in a 1:1 ratio to receive istradefylline (20 mg/day, escalating to 40 mg/day) or no istradefylline (control). Subitems of the MDS-UPDRS and the PDQ-39 were evaluated.

Results: A total of 105 patients (istradefylline group = 52, control group = 53) were included in the efficacy analyses. Regarding the MDS-UPDRS subitems, daytime sleepiness (1.8), fatigue (1.13), doing hobbies and other activities (2.8), facial expression (3.2), rigidity (3.3), finger tapping (3.4), toe tapping (3.7), time spent in the off state (4.3), and complexity of motor fluctuations (4.5) were significantly improved in the istradefylline group and, rigidity (3.3), time spent in the off state (4.3), and functional impact of fluctuations (4.4) were significantly improved in the control group. Evaluation of PDQ-39 subitems demonstrated a significant improvement in scores related to doing up buttons or shoelaces (13), writing (14), feeling angry or bitter (20), and unexpectedly falling asleep during the day (30) only in the istradefylline group.

Conclusion: Istradefylline significantly improved motor symptoms as well as non-motor symptoms such as daytime sleepiness, fatigue, and several PDQ-39 subitems. The improvement of these symptoms may be achieved with istradefylline rather than levodopa dose increase.

References: [1] T. Hatano, O. Kano, R. Sengoku, N. Yanagisawa, H. Nagayama. Impact of istradefylline on the adjustment of levodopa dose escalation in Parkinson’s disease: Results of the ISTRA ADJUST PD randomized, controlled study [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/impact-of-istradefylline-on-the-adjustment-of-levodopa-dose-escalation-in-parkinsons-disease-results-of-the-istra-adjust-pd-randomized-controlled-study/. Accessed January 15, 2024.

[2] T. Hatano, R. Sengoku, H. Nagayama, et al. Impact of istradefylline on levodopa dose escalation in Parkinson’s disease: ISTRA ADJUST PD study, a multi-center, open-label, randomized, parallel-group, controlled study. Neurol Ther, doi: 10.1007/s40120-023-00574-6. Online ahead of print..

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effect-of-istradefylline-on-motor-and-non-motor-symptoms-in-patients-with-parkinsons-disease-the-istra-adjust-pd-randomized-controlled-study/