Istradefylline 对帕金森病患者运动和非运动症状的影响：ISTRA ADJUST帕金森病子分析

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders Pub Date : 2025-01-01 DOI:10.1016/j.prdoa.2025.100327

Hiroshi Nagayama , Osamu Kano , Renpei Sengoku , Naotake Yanagisawa , Asako Yoritaka , Keisuke Suzuki , Noriko Nishikawa , Yohei Mukai , Kyoichi Nomura , Norihito Yoshida , Morinobu Seki , Miho Kawabe Matsukawa , Hiroo Terashi , Katsuo Kimura , Jun Tashiro , Shigeki Hirano , Hidetomo Murakami , Hideto Joki , Tsuyoshi Uchiyama , Hideki Shimura , Taku Hatano

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引用次数: 0

摘要

帕金森病（PD）表现为多种运动和非运动症状，其中一些症状对多巴胺替代治疗不完全有效。为了阐明腺苷A2A受体拮抗剂iststradefylline （IST）对PD症状的影响，我们对为期37周的ISTRA ADJUST PD随机对照试验进行了亚分析。方法左旋多巴剂量为300 ~ 400 mg/d的PD患者，按1:1随机分为IST组和不IST组（对照组）。在整个研究过程中，左旋多巴剂量根据临床严重程度进行滴定。采用运动障碍学会统一帕金森病评定量表（MDS-UPDRS）和帕金森病问卷-39 （PDQ-39）对帕金森病症状进行评估。结果纳入疗效分析105例(IST, n = 52；对照组，n = 53)。IST组患者的MDS-UPDRS分项有显著改善(p <；与基线相比，第36周观察到运动（如面部表情、僵硬、手指敲打、脚趾敲打、处于关闭状态的时间和运动波动的复杂性）和非运动（如白天嗜睡、疲劳、从事爱好和其他活动）症状。在对照组患者中，显著改善(p <；仅在运动症状中观察到0.05)。IST组患者的PDQ-39分项有显著改善(p <；在扣扣子或系鞋带、写作、感到愤怒或痛苦以及白天意外入睡方面，与基线相比，观察到0.05)。结论ist能改善运动和非运动症状及生活质量，提示其对PD症状的改善比单独增加左旋多巴剂量更全面。临床试验注册：日本临床试验注册中心；研究编号：jRCTs031180248。

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Impact of istradefylline on motor and non-motor symptoms in patients with Parkinson’s disease: Subanalysis of the ISTRA ADJUST PD

Introduction

Parkinson’s disease (PD) presents with diverse motor and non-motor symptoms, some of which do not fully respond to dopamine replacement therapy. To clarify the effects of the adenosine A_2A receptor antagonist istradefylline (IST) on PD symptoms, we conducted a subanalysis of the 37-week ISTRA ADJUST PD randomized controlled trial.

Methods

Patients with PD experiencing wearing-off with levodopa at 300–400 mg/day were randomized 1:1 to receive IST or no IST (control). Levodopa doses were titrated according to clinical severity throughout the study. PD symptoms were assessed using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Parkinson’s Disease Questionnaire-39 (PDQ-39).

Results

The efficacy analyses included 105 patients (IST, n = 52; control, n = 53). Regarding MDS-UPDRS subitems in patients in the IST group, significant improvements (p < 0.05) were observed at week 36 compared with baseline for both motor (e.g., facial expression, rigidity, finger tapping, toe tapping, time spent in the off state, and complexity of motor fluctuation) and non-motor (e.g., daytime sleepiness, fatigue, and doing hobbies and other activities) symptoms. In patients in the control group, significant improvements (p < 0.05) were observed for motor symptoms only. Regarding PDQ-39 subitems in patients in the IST group, significant improvements (p < 0.05) were observed at week 36 compared with baseline in doing up buttons or shoelaces, writing, feeling angry or bitter, and unexpectedly falling asleep during the day.

Conclusion

IST can improve motor and non-motor symptoms and quality of life suggesting that it provides more comprehensive improvement in PD symptoms than increasing the levodopa dose alone.