Impact of Adjunctive Istradefylline on Dyskinesia Onset in Patients with Parkinson's Disease Exhibiting Wearing-Off: An Open-Label Randomized Controlled Trial.

IF 4.8 3区医学 Q1 CLINICAL NEUROLOGY

Neurology and Therapy Pub Date : 2025-09-24 DOI:10.1007/s40120-025-00809-8

Yoshio Tsuboi, Takafumi Hasegawa, Yasushi Shimo, Satoshi Kaneko, Masahiko Tomiyama, Kenichi Kashihara, Shih-Wei Chiu, Takuhiro Yamaguchi

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引用次数: 0

Abstract

Introduction: Motor complications become major treatment challenges in patients with Parkinson's disease (PD). Istradefylline (IST) is used as an adjunct to levodopa in patients with PD exhibiting wearing-off (WO), but its impact on the onset of dyskinesia remains unclear. The objective of this study was to investigate the effect of IST on dyskinesia onset in patients with PD exhibiting WO.

Methods: In this 3-year, multicenter, randomized, open-label, parallel-group, controlled study, 214 patients with levodopa-treated PD exhibiting WO without pre-existing dyskinesia were randomized (1:1) to either adjunctive IST (IST group) or to adding another or increasing the dose of other anti-PD drugs (non-IST group). The primary endpoint was the time to onset of dyskinesia.

Results: Over 3 years, the incidence of dyskinesia was 37.9% and 41.1% in the IST and non-IST groups, respectively. The time to onset of dyskinesia was not significantly different between the IST versus non-IST groups (median: 1100.00 vs. 1082.00 days). When dividing patients by age, the rate of time to onset of dyskinesia was lower in the IST group in patients aged ≥ 68 years (median) and in the non-IST group for patients aged < 68 years and patients aged < 60 years at PD onset. The levodopa-equivalent daily dose (LEDD) was significantly lower throughout the study period, by 57 mg on average, in the IST group than in the non-IST group. Efficacy and safety indexes were not significantly different between the two groups.

Conclusion: Adjunctive IST showed no difference in the onset of dyskinesia compared with adding another or increasing the dose of other anti-PD drugs, and displayed equivalent efficacy and tolerability, while maintaining a lower LEDD in this long-term study of patients with PD exhibiting WO. These findings support the use of adjunctive IST as a viable treatment option for patients with PD exhibiting WO.

Trial registration: University hospital Medical Information Network clinical trials registry (UMIN000024536) and Japan Registry of Clinical Trials (jRCTs071180014).

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辅助伊斯特福林对帕金森病患者运动障碍发作的影响：一项开放标签随机对照试验。

运动并发症成为帕金森病（PD）患者治疗的主要挑战。isstradefylline （IST）被用作左旋多巴的辅助药物用于PD患者表现出磨损（WO），但其对运动障碍发病的影响尚不清楚。本研究的目的是探讨IST对表现为WO的PD患者运动障碍发作的影响。方法：在这项为期3年的多中心、随机、开放标签、平行组、对照研究中，214例左旋多巴治疗的无运动障碍的PD患者被随机（1:1）分配到辅助IST组（IST组）或添加或增加其他抗PD药物的剂量（非IST组）。主要终点是出现运动障碍的时间。结果：3年内，IST组和非IST组运动障碍发生率分别为37.9%和41.1%。IST组与非IST组的运动障碍发病时间无显著差异（中位数：11000.00 vs 1082.00天）。按年龄分组时，≥68岁患者IST组（中位数）和老年患者非IST组（中位数）出现运动障碍的时间比IST组低。结论：在本长期研究中，辅助IST与添加其他抗PD药物或增加剂量相比，在出现运动障碍的PD患者中表现出相同的疗效和耐受性，同时保持较低的LEDD。这些发现支持使用辅助IST作为PD患者出现WO的可行治疗选择。试验注册：大学医院医学信息网临床试验注册（UMIN000024536）和日本临床试验注册（jRCTs071180014）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurology and Therapy CLINICAL NEUROLOGY-

CiteScore

5.40

自引率

8.10%

发文量

103

审稿时长

6 weeks

期刊介绍： Aims and Scope Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice. Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial designs, communications and letters. 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