Efficacy and Tolerability of Entacapone as Adjunctive Therapy to Levodopa in Patients with Parkinson’s Disease and End-of-Dose Deterioration in Daily Medical Practice: An Open, Multicenter Study
Efficacy and Tolerability of Entacapone as Adjunctive Therapy to Levodopa in Patients with Parkinson’s Disease and End-of-Dose Deterioration in Daily Medical Practice: An Open, Multicenter Study
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恩他卡朋作为左旋多巴辅助治疗对日常医疗实践中帕金森病和剂量结束恶化患者的疗效和耐受性：一项开放、多中心研究
DOI：
10.1159/000052104
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发表时间：
2001
影响因子：
2.4
通讯作者：
I. Bourdeix
中科院分区：
文献类型：
--
作者：
Franck Durif;I. Devaux;J. Pere;J. Delumeau;I. Bourdeix
恩他卡朋是一种有效的、可逆的和口服活性的儿茶酚-O-甲基转移酶抑制剂。这项开放性多中心研究评价了恩他卡朋作为左旋多巴/多巴脱羧酶抑制剂（每日103次剂量）的辅助治疗在特发性帕金森病和剂量终末运动波动患者中的疗效、安全性和耐受性。这项为期8周的研究包括489名患者，这些患者处于典型的日常医疗实践条件下。患者接受200 mg固定剂量的恩他卡朋治疗，与每个预定剂量的左旋多巴一起给药，每天最多给药10次。其他抗帕金森病药物应稳定至少1个月。主要有效性标准为：（1）统一帕金森病评定量表（CIMRS）的第II部分（日常生活活动，ADL），（2）通过CIMRS第IV部分第39项中至少一个类别改善的患者百分比评估的每日清醒期间“休息”时间减少。次要结局指标包括：（1）研究者对变化的总体评估，（2）使用帕金森病问卷（PDQ-39）评估生活质量（QoL）。在第2周和第8周监测不良事件、生命体征和肝酶。ADL的基线平均评分为10.5（±7.04），在研究结束时降至8.5（±6.37）（p < 0.0001）。与基线相比，40.8%的患者在清醒期间经历了“关闭”时间的减少;这种改善非常显著（p < 0.0001）。在35.8%的患者中观察到左旋多巴日剂量减少（平均减少209 ± 149 mg）。除社会支持和认知外，PDQ-39所有类别的QoL平均改善10%（p < 0.001）。这种改善具有统计学显著性（p < 0.001）。从基线到研究结束时，运动障碍评分（ADRS项目32）从2.3显著降低至2.1（p < 0.001），尽管52.7%的患者报告左旋多巴诱导的运动障碍为不良事件。无肝酶升高病例。研究结果证实，在III期对照研究中观察到的极好的风险/获益比可以在日常神经病学实践中观察到。此外，该研究表明恩他卡朋的益处与QoL的显著改善相关。
Entacapone is a potent, reversible and orally active inhibitor of catechol-O-methyltransferase. This open multicenter study evaluated the efficacy, safety and tolerability of entacapone as adjunct therapy to levodopa/dopa decarboxylase inhibitor (≧3 daily doses) in patients with idiopathic Parkinson’s disease and end-of-dose motor fluctuations. The 8-week study included 489 patients under conditions of typical daily medical practice. Patients were treated with a 200-mg fixed dose of entacapone administered with each scheduled dose of levodopa to a maximum of 10 doses per day. Other antiparkinsonian medication should have been stable for at least 1 month. The primary efficacy criteria were: (1) Part II (activities of daily living, ADL) of the Unified Parkinson’s Disease Rating Scale (UPDRS), (2) the reduction of ‘off’ time during the daily waking period as assessed by the percentage of patients improving by at least one category at Item 39 of Part IV of the UPDRS. Secondary outcome measures included: (1) the investigator’s global assessment of change, (2) quality of life (QoL) was assessed using the Parkinson’s Disease Questionnaire (PDQ-39). Adverse events, vital signs and liver enzymes were monitored at weeks 2 and 8. The baseline mean score for ADL was 10.5 (±7.04), which decreased to 8.5 (±6.37) at the end of the study (p < 0.0001). Compared to baseline, 40.8% of patients experienced a reduction in ‘off’ time during the waking period; this improvement was highly significant (p < 0.0001). A reduction in the daily dose of levodopa was observed in 35.8% of patients (mean decrease 209 ± 149 mg). QoL was improved by a mean of 10% in all categories of the PDQ-39 (p < 0.001), except social support and cognition. This improvement was statistically significant (p < 0.001). The dyskinesia score (UPDRS Item 32) was decreased significantly from 2.3 to 2.1 from baseline to end of study (p < 0.001), although 52.7% of patients reported levodopa-induced dyskinesia as an adverse event. There was no case of increased liver enzymes. The study results confirm that the excellent risk/benefit ratio seen in phase III controlled studies can be seen in daily neurological practice. Moreover, the study suggests that the benefits of entacapone are associated with a significant improvement in QoL.