Virhammar Johan, Nyholm Dag
Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
Department of Neuroscience, Neurology, Uppsala University Hospital, 751 85 Uppsala, Sweden.
Ther Adv Neurol Disord. 2017 Mar;10(3):171-187. doi: 10.1177/1756285616681280. Epub 2016 Dec 1.
The duration of action of oral levodopa becomes shorter as Parkinson's disease (PD) progresses. Patients with advanced PD may develop potentially disabling motor fluctuations and abnormal involuntary movement (dyskinesia), which cannot be managed with optimized oral or transdermal PD medications. The progressively worsening symptoms can have a substantial impact on the patient quality of life (QoL). Levodopa-carbidopa intestinal gel (LCIG) is delivered continuously a percutaneous endoscopic gastrostomy with a jejunal extension (PEG-J). LCIG is licensed for the treatment of levodopa-responsive advanced PD in individuals experiencing severe motor fluctuations and dyskinesia when available combinations of antiparkinsonian medications have not given satisfactory results. Initial evidence for the efficacy and tolerability of LCIG came from a number of small-scale studies, but recently, three prospective studies have provided higher quality evidence. A 12-week double-blind comparison of LCIG with standard levodopa therapy, a 52-week open-label study extension of the double-blind study, and a 54-week open-label safety study, demonstrated significant improvements in 'off' time and 'on' time without troublesome dyskinesia, and QoL measures that were maintained in the longer term. There are also observations that LCIG may be effective treatment for nonmotor symptoms (NMS) although the evidence is limited. There is a need for further research on the efficacy of LCIG in reducing NMS, dyskinesia and improving QoL. This review surveys the clinical evidence for the effectiveness and tolerability of LCIG in the management of advanced PD and highlights some practical considerations to help optimize treatment.
随着帕金森病(PD)的进展,口服左旋多巴的作用持续时间会缩短。晚期帕金森病患者可能会出现潜在致残性的运动波动和异常不自主运动(异动症),而优化后的口服或经皮帕金森病药物无法对其进行有效控制。症状的逐渐恶化会对患者的生活质量(QoL)产生重大影响。左旋多巴-卡比多巴肠凝胶(LCIG)通过经皮内镜下胃造口术并带有空肠延长管(PEG-J)持续给药。LCIG被批准用于治疗对左旋多巴有反应的晚期帕金森病,适用于那些在使用现有抗帕金森病药物组合未取得满意效果、出现严重运动波动和异动症的患者。LCIG疗效和耐受性的初步证据来自一些小规模研究,但最近有三项前瞻性研究提供了更高质量的证据。一项将LCIG与标准左旋多巴疗法进行的为期12周的双盲比较研究、该双盲研究为期52周的开放标签研究扩展以及一项为期54周的开放标签安全性研究表明,“关”期时间和“开”期时间有显著改善,且无烦人的异动症,生活质量指标在长期内得以维持。也有观察结果表明,尽管证据有限,但LCIG可能对非运动症状(NMS)有效。需要进一步研究LCIG在减轻非运动症状、异动症及改善生活质量方面的疗效。本综述调查了LCIG在治疗晚期帕金森病方面有效性和耐受性的临床证据,并强调了一些有助于优化治疗的实际考虑因素。