Lang Anthony E, Rodriguez Ramon L, Boyd James T, Chouinard Sylvain, Zadikoff Cindy, Espay Alberto J, Slevin John T, Fernandez Hubert H, Lew Mark F, Stein David A, Odin Per, Fung Victor S C, Klostermann Fabian, Fasano Alfonso, Draganov Peter V, Schmulewitz Nathan, Robieson Weining Z, Eaton Susan, Chatamra Krai, Benesh Janet A, Dubow Jordan
Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital and Division of Neurology, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
University of Florida College of Medicine, Gainesville, Florida, USA.
Mov Disord. 2016 Apr;31(4):538-46. doi: 10.1002/mds.26485. Epub 2015 Dec 23.
Continuous administration of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) through a percutaneous endoscopic gastrojejunostomy is a treatment option for advanced Parkinson disease (PD) patients with motor fluctuations resistant to standard oral medications. Safety data from 4 prospective studies were integrated to assess the safety of this therapy.
Safety data from 4 studies were summarized using 2 overlapping data sets, permitting the separation of procedure/device-associated (n = 395) from non-procedure/device adverse events (n = 412).
At the data cutoff, median exposure to levodopa-carbidopa intestinal gel was 911 days (range, 1-1980 days) with 963 total patient-years of exposure. Procedure/device adverse events occurred in 300 patients (76%), and serious adverse events occurred in 68 (17%); most frequently reported procedure/device adverse events and serious adverse events were complications of device insertion (41% and 8%, respectively) and abdominal pain (36% and 4%, respectively). Non-procedure/device adverse events occurred in 92% (379), with most frequently reported being insomnia (23%) and falls (23%); 42% (171) had non-procedure/device serious adverse events, with most frequently reported being pneumonia (5%) and PD symptoms (2%). Adverse events led to discontinuation in 17% (72), most frequently because of complication of device insertion (2.4%). There were 34 treatment-emergent deaths (8.3%) in the overlapping data sets, 2 of which (0.5%) were considered "possibly related" to the treatment system.
In the largest collection of levodopa-carbidopa intestinal gel safety data from prospective clinical studies, procedure/device events were frequently reported and occasionally life threatening. Most non-procedure/device events were typical for levodopa treatment and an elderly population. These factors combined with high treatment efficacy led to a relatively low discontinuation rate in advanced PD patients.
对于对标准口服药物产生运动波动的晚期帕金森病（PD）患者，通过经皮内镜下胃空肠造口术持续给予左旋多巴-卡比多巴肠凝胶（卡比多巴-左旋多巴肠内混悬液）是一种治疗选择。整合了4项前瞻性研究的安全性数据以评估该疗法的安全性。
使用2个重叠数据集总结4项研究的安全性数据，从而能够将与手术/器械相关的不良事件（n = 395）与非手术/器械不良事件（n = 412）区分开来。
在数据截止时，左旋多巴-卡比多巴肠凝胶的中位暴露时间为911天（范围为1 - 1980天），总暴露患者年数为963。300例患者（76%）发生了与手术/器械相关的不良事件，68例（17%）发生了严重不良事件；最常报告的与手术/器械相关的不良事件和严重不良事件分别是器械插入并发症（分别为41%和8%）和腹痛（分别为36%和4%）。92%（379例）发生了非手术/器械不良事件，最常报告的是失眠（23%）和跌倒（23%）；42%（171例）发生了非手术/器械严重不良事件，最常报告的是肺炎（5%）和PD症状（2%）。不良事件导致17%（72例）停药，最常见的原因是器械插入并发症（2.4%）。在重叠数据集中有34例治疗中出现的死亡（8.3%），其中2例（0.5%）被认为“可能与”治疗系统“相关”。
在前瞻性临床研究中关于左旋多巴-卡比多巴肠凝胶安全性数据的最大规模汇总中，与手术/器械相关的事件经常被报告，偶尔会危及生命。大多数非手术/器械相关事件是左旋多巴治疗和老年人群中常见的。这些因素与高治疗效果相结合，导致晚期PD患者的停药率相对较低。
