缓释戈柯夫里（金刚烷胺）胶囊对帕金森病伴运动障碍患者非运动症状的影响。
Effects of Gocovri (Amantadine) Extended Release Capsules on Non-Motor Symptoms in Patients with Parkinson's Disease and Dyskinesia.
作者信息
Mehta Shyamal H, Pahwa Rajesh, Tanner Caroline M, Hauser Robert A, Johnson Reed
机构信息
Department of Neurology, Mayo Clinic-Scottsdale, 13400 East Shea Blvd, Scottsdale, AZ, 85254, USA.
Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
出版信息
Neurol Ther. 2021 Jun;10(1):307-320. doi: 10.1007/s40120-021-00246-3. Epub 2021 Apr 17.
INTRODUCTION
Gocovri (amantadine) extended release capsules are approved for treatment of dyskinesia and as a levodopa adjunct for OFF episodes in patients with Parkinson's disease (PD). We report treatment-related effects on non-motor symptoms (NMS) assessed as secondary outcomes in two trials using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I.
METHODS
EASE LID and EASE LID 3 enrolled levodopa-treated patients with PD and ≥ 1 h/day ON time with troublesome dyskinesia. Patients were randomized to Gocovri (274 mg) or placebo taken daily at bedtime. Treatment differences from baseline to week 12 in MDS-UPDRS Part I were evaluated for the pooled population (N = 196) from both trials. Correlation analyses of NMS (MDS-UPDRS Part I) with dyskinesia using Unified Dyskinesia Rating Scale (UDysRS) scores were performed.
RESULTS
For changes in the MDS-UPDRS Part I items, the treatment difference favored Gocovri in daytime sleepiness (P = 0.006) and depression (P = 0.049) scores, but favored placebo in cognitive impairment (P = 0.038), and hallucinations and psychosis (P < 0.001) scores. The treatment difference for the changes in total Part I score was -0.8, favoring Gocovri (P = 0.22). At baseline, MDS-UPDRS Part I modestly correlated with UDysRS score (r +0.25, P < 0.001), and improvement in NMS correlated with improvement in dyskinesia at week 12 for Gocovri (r +0.39, P < 0.001) but not placebo (r +0.12, P = 0.29). The most commonly reported adverse events for Gocovri were hallucination (21%); dizziness, dry mouth, and peripheral edema (16% each); and constipation, falls, and orthostatic hypotension (13% each).
CONCLUSION
This post hoc analysis shows potential benefit with Gocovri treatment for the NMS of daytime sleepiness and depression in dyskinetic PD patients. Overall, improvement in NMS scores correlated with improvement in dyskinesia.
TRIAL REGISTRATION
ClinicalTrials.gov identifiers: NCT02136914 and NCT02274766.
引言
缓释型Gocovri（金刚烷胺）胶囊已获批用于治疗帕金森病（PD）患者的运动障碍，并作为左旋多巴的辅助药物用于“关”期发作。我们报告了在两项试验中，使用运动障碍协会统一帕金森病评定量表（MDS-UPDRS）第一部分评估的与治疗相关的对非运动症状（NMS）的影响，这些影响作为次要结果。
方法
EASE LID和EASE LID 3纳入了接受左旋多巴治疗、每日“开”期时间≥1小时且伴有严重运动障碍的PD患者。患者被随机分为Gocovri（274毫克）组或安慰剂组，每天睡前服用。对两项试验的合并人群（N = 196）评估从基线到第12周MDS-UPDRS第一部分的治疗差异。使用统一运动障碍评定量表（UDysRS）评分对NMS（MDS-UPDRS第一部分）与运动障碍进行相关性分析。
结果
对于MDS-UPDRS第一部分项目的变化，治疗差异在白天嗜睡（P = 0.006）和抑郁（P = 0.049）评分方面有利于Gocovri，但在认知障碍（P = 0.038）以及幻觉和精神病（P < 0.001）评分方面有利于安慰剂。第一部分总分变化的治疗差异为-0.8，有利于Gocovri（P = 0.22）。在基线时，MDS-UPDRS第一部分与UDysRS评分适度相关（r = +0.25，P < 0.001），对于Gocovri，第12周时NMS的改善与运动障碍的改善相关（r = +0.39，P < 0.001），而安慰剂组则无相关性（r = +0.12，P = 0.29）。Gocovri最常报告的不良事件为幻觉（21%）；头晕、口干和外周水肿（各16%）；以及便秘、跌倒和体位性低血压（各13%）。
结论
这项事后分析表明，Gocovri治疗对运动障碍型PD患者的白天嗜睡和抑郁等非运动症状具有潜在益处。总体而言，非运动症状评分的改善与运动障碍的改善相关。
试验注册
ClinicalTrials.gov标识符：NCT02136914和NCT02274766。
Zotero 插件