Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.
Mov Disord. 2013 Jul;28(8):1064-71. doi: 10.1002/mds.25364. Epub 2013 Apr 29.
The Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE-PD) study compared the initiation of levodopa (l-dopa) therapy with l-dopa/carbidopa (LC) versus l-dopa/carbidopa/entacapone (LCE) in patients with Parkinson's disease. In the current study, the STRIDE-PD study population was investigated to determine the effect of l-dopa dose and other risk factors on the development of dyskinesia and wearing-off. Patients were randomized to receive LCE (n=373) or LC (n=372). Blinded assessments for dyskinesia and wearing-off were performed at 3-month intervals for the 134- to 208-week duration of the study. The patients were divided into 4 dose groups based on nominal l-dopa dose at the time of onset of dyskinesia (or at study conclusion if there was no dyskinesia): group 1, <400 mg/day (n=157); group 2, 400 mg/day (n=310); group 3, 401 to 600 mg/day (n=201); and group 4, >600 mg/day (n=77). Similar analyses were performed with respect to wearing-off and any motor complication. The times to onset and frequency of dyskinesia, wearing-off, or any motor complication were compared using the log-rank test (overall trend test) and a Cox proportional hazards model (pairwise comparisons). A stepwise Cox proportional hazards model was used to screen predictive factors in a multivariate analysis. The risk of developing dyskinesia and wearing-off increased in an l-dopa dose-dependent manner (P<0.001 for both). Analyses using l-dopa equivalent doses produced comparable results. Factors that were predictive of dyskinesia, in rank order, were: young age at onset, higher l-dopa dose, low body weight, North American geographic region, LCE treatment group, female gender, and more severe Unified Parkinson's Disease Rating Scale (UPDRS) Part II. Multivariate analyses identified similar predictors for wearing-off but included baseline UPDRS Part III and excluded weight and treatment allocation. The risk of developing dyskinesia or wearing-off was closely linked to l-dopa dose. The current results suggest that physicians should use the lowest dose of l-dopa that provides satisfactory clinical control to minimize the risk of both dyskinesia and wearing-off.
左旋多巴治疗帕金森病中减少异动症的评价研究（STRIDE-PD）比较了左旋多巴（L-dopa）治疗开始时给予左旋多巴/卡比多巴（LC）与左旋多巴/卡比多巴/恩他卡朋（LCE）在帕金森病患者中的效果。在本研究中，研究人员对 STRIDE-PD 研究人群进行了调查，以确定 L-dopa 剂量和其他风险因素对异动症和开-关现象发展的影响。患者被随机分配接受 LCE（n=373）或 LC（n=372）治疗。在研究的 134-208 周期间，每 3 个月进行一次对异动症和开-关现象的盲法评估。根据异动症发生时（或无异动症时研究结束时）的名义 L-dopa 剂量，患者被分为 4 个剂量组：组 1，<400 mg/天（n=157）；组 2，400 mg/天（n=310）；组 3，401-600 mg/天（n=201）；组 4，>600 mg/天（n=77）。对开-关现象和任何运动并发症也进行了类似的分析。使用对数秩检验（整体趋势检验）和 Cox 比例风险模型（成对比较）比较了异动症、开-关现象或任何运动并发症的发生时间和频率。使用逐步 Cox 比例风险模型进行多变量分析筛选预测因素。发展异动症和开-关现象的风险呈 L-dopa 剂量依赖性增加（两者均 P<0.001）。使用 L-dopa 等效剂量进行的分析产生了类似的结果。按等级排列，预测异动症的因素依次为：发病年龄较轻、较高的 L-dopa 剂量、较低的体重、北美地理区域、LCE 治疗组、女性性别和更严重的帕金森病统一评定量表（UPDRS）第二部分。多变量分析确定了开-关现象的类似预测因素，但包括基线 UPDRS 第三部分，排除了体重和治疗分配。发展异动症或开-关现象的风险与 L-dopa 剂量密切相关。目前的结果表明，医生应使用提供满意临床控制的最低剂量的 L-dopa，以最大程度降低异动症和开-关现象的风险。
