左旋多巴-卡比多巴肠凝胶治疗帕金森病患者：一项为期12个月的开放性研究结果

[Levodopa-carbidopa intestinal gel in the treatment of patients with Parkinson disease: results of a 12-month open study].

作者信息

Skoromets A A, Odinak M M, Yakupov E Z, Litvinenko I V, Zalyalova Z A, Timofeeva A A, Kirtaev S Yu, Bogdanov R R, Agafina A S, Chatamra K, Robieson W, Benesh J, Latypova G R, Ershova M V, Illarioshkin S N

机构信息

Pavlov First St.-Petersburg State Medical University, St.-Petersburg.

Kirov Military Medical Academy, St.-Petersburg.

出版信息

Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(2):22-31. doi: 10.17116/jnevro20171172122-31.

DOI:10.17116/jnevro20171172122-31

PMID:28374689

Abstract

AIM

To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs.

MATERIAL AND METHODS

A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of "off" periods, "on" periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D и EQ-VAS) dynamics, an analysis of patient's diaries) were assessed throughout the whole study.

RESULTS

The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of "off" periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of "on" periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of "on" periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study.

CONCLUSION

LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction.

摘要

目的

评估空肠内左旋多巴-卡比多巴肠凝胶（LCIG）输注治疗对口服药物治疗反应欠佳的晚期帕金森病（PD）患者的长期安全性和疗效。

材料与方法

开展一项关于LCIG治疗伴有严重运动波动的PD患者的大规模国际前瞻性开放标签54周研究。俄罗斯共纳入48例患者，46例（95.8%）置入了经皮内镜下胃造口-空肠造口术（PEG-J），其中43例完成研究。在整个研究过程中评估安全性，包括不良事件（AE）、输注系统和泵故障分析、完全终止研究的患者数量，以及疗效（“关”期时长、有或无麻烦异动症的“开”期时长、统一帕金森病评定量表（UPDRS）评分、临床总体印象、生活质量（帕金森病问卷-39、欧洲五维健康量表（EQ-5D）及视觉模拟量表（EQ-VAS））动态变化、患者日记分析）。

结果

大多数AE为轻度或中度，多数AE与输注系统应用有关（28.3%的患者），包括操作疼痛。8例患者（16.7%）出现严重AE。3例患者（6.3%）因AE停止参与研究。研究结束时，“关”期平均时长减少5.35±2.59小时（p<0.001），无麻烦异动症的“开”期时长增加5.74±,3.91小时（p<0.001），有麻烦异动症的“开”期时长在第36周时缩短具有统计学意义（p=0.020）。在整个研究过程中观察到UPDRS（总体及各子量表）、临床总体印象和生活质量评分有统计学意义的改善。在54周的治疗期间，左旋多巴剂量保持稳定。43例患者（93.5%）在整个研究过程中接受LCIG单药治疗。