Antonini Angelo, Fung Victor S C, Boyd James T, Slevin John T, Hall Coleen, Chatamra Krai, Eaton Susan, Benesh Janet A
Parkinson and Movement Disorders Unit, IRCCS Hospital San Camillo, Venice, Italy.
Movement Disorders Unit, Westmead Hospital and Sydney Medical School, Sydney, Australia.
Mov Disord. 2016 Apr;31(4):530-7. doi: 10.1002/mds.26528. Epub 2016 Jan 28.
The purpose of this study was to assess the effect of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) in advanced Parkinson's disease patients with troublesome dyskinesia.
Post hoc analyses of patient data from a 12-week, randomized, double-blind study and a 54-week open-label study were performed. Efficacy was assessed in the subgroup of patients defined by ≥1 hour of "on" time with troublesome dyskinesia at baseline as recorded in Parkinson's disease symptom diaries (double blind: n = 11 levodopa-carbidopa intestinal gel, n = 12 oral levodopa-carbidopa; open label: n = 144 levodopa-carbidopa intestinal gel). The changes in "off" time, "on" time with and without troublesome dyskinesia, and the overall safety and tolerability of levodopa-carbidopa intestinal gel were analyzed.
Although not significantly different from oral levodopa treatment (P > .05) in the double-blind study, levodopa-carbidopa intestinal gel treatment resulted in a reduction from baseline in "on" time with troublesome dyskinesia (mean [standard deviation] hours: baseline = 3.1 [1.7], change from baseline to final = -1.8 [1.8], P = .014), increase in "on" time without troublesome dyskinesia (baseline = 7.4 [2.2], change = 4.4 [3.6], P = .004), and decrease in "off" time (baseline = 5.5 [1.3], change = -2.7 [2.8], P = .015). Similar trends were found in the open-label study. An increase in levodopa-carbidopa intestinal gel dose was not significantly correlated with increased "on" time with troublesome dyskinesia in either study (double blind: r = -.073, P = .842; open label: r = -0.001, P = .992). Adverse events were usually mild to moderate in severity and related to the gastrointestinal procedure.
Our exploratory analyses suggest that optimizing levodopa delivery with levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson's disease.
本研究旨在评估左旋多巴-卡比多巴肠凝胶（卡比多巴-左旋多巴肠内混悬液）对患有严重运动障碍的晚期帕金森病患者的疗效。
对一项为期12周的随机双盲研究和一项为期54周的开放标签研究中的患者数据进行事后分析。在帕金森病症状日记中记录的基线时“开”期伴有严重运动障碍≥1小时的患者亚组中评估疗效（双盲：n = 11例左旋多巴-卡比多巴肠凝胶，n = 12例口服左旋多巴-卡比多巴；开放标签：n = 144例左旋多巴-卡比多巴肠凝胶）。分析了“关”期时间、伴有和不伴有严重运动障碍的“开”期时间的变化，以及左旋多巴-卡比多巴肠凝胶的总体安全性和耐受性。
在双盲研究中，尽管与口服左旋多巴治疗相比无显著差异（P > 0.05），但左旋多巴-卡比多巴肠凝胶治疗使伴有严重运动障碍的“开”期时间较基线减少（平均[标准差]小时：基线 = 3.1 [1.7]，从基线到最终的变化 = -1.8 [1.8]，P = 0.014），无严重运动障碍的“开”期时间增加（基线 = 7.4 [2.2]，变化 = 4.4 [3.6]，P = 0.004），“关”期时间减少（基线 = 5.5 [1.3]，变化 = -2.7 [2.8]，P = 0.015）。在开放标签研究中也发现了类似趋势。在两项研究中，左旋多巴-卡比多巴肠凝胶剂量的增加与伴有严重运动障碍的“开”期时间增加均无显著相关性（双盲：r = -0.073，P = 0.842；开放标签：r = -0.001，P = 0.992）。不良事件通常为轻度至中度，且与胃肠道操作有关。
我们的探索性分析表明，用左旋多巴-卡比多巴肠凝胶优化左旋多巴给药可能减少晚期帕金森病中的严重运动障碍。
