Zadikoff Cindy, Poewe Werner, Boyd James T, Bergmann Lars, Ijacu Horia, Kukreja Pavnit, Robieson Weining Z, Benesh Janet, Antonini Angelo
AbbVie Inc., North Chicago, Illinois, USA.
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Parkinsons Dis. 2020 Feb 13;2020:9716317. doi: 10.1155/2020/9716317. eCollection 2020.
Levodopa-carbidopa intestinal gel (LCIG) provides continuous levodopa administration and clinical benefits to patients with advanced Parkinson's disease (PD). This report evaluates long-term safety and efficacy of high-dose LCIG in PD patients.
Data were collected from several prospective, phase III clinical studies and an observational registry. The phase III program ( = 412) included four multicenter studies: a 12-week, randomized, double-blind study and three open-label studies extending ≥12 months. GLORIA ( = 412) included four multicenter studies: a 12-week, randomized, double-blind study and three open-label studies extending ≥12 months. GLORIA (.
A total of 72 of 412 (17.5%) patients required dosages ≥2000 mg/day LCIG in the phase III program and 47 of 375 (12.5%) patients in GLORIA. Baseline demographics and disease severity were similar between dosage groups with more men in the high-dosage group. Compared with the <2000 mg/day dosage group, patients requiring ≥2000 mg/day LCIG had higher rates of AEs/ADRs including polyneuropathy; improvements in "Off" time and discontinuations due to AEs were similar between dosage groups and lower for discontinuations due to ADRs reported in GLORIA.
Patients who require ≥2000 mg/day LCIG exhibited a safety profile comparable to the established safety/tolerability of LCIG with similar clinical improvements. Higher AEs were noted but within what is accepted for LCIG. Continuous administration of LCIG is beneficial to advanced PD patients who require very high doses of levodopa.
左旋多巴-卡比多巴肠凝胶（LCIG）可为晚期帕金森病（PD）患者提供持续的左旋多巴给药并带来临床益处。本报告评估了高剂量LCIG在PD患者中的长期安全性和有效性。
数据收集自多项前瞻性III期临床研究和一个观察性登记处。III期项目（n = 412）包括四项多中心研究：一项为期12周的随机双盲研究和三项为期≥12个月的开放标签研究。GLORIA（n = 412）包括四项多中心研究：一项为期12周的随机双盲研究和三项为期≥12个月的开放标签研究。GLORIA（......）。
在III期项目中，412例患者中有72例（17.5%）需要≥2000 mg/天的LCIG剂量，在GLORIA中，375例患者中有47例（12.5%）需要该剂量。剂量组之间的基线人口统计学和疾病严重程度相似，高剂量组男性更多。与<2000 mg/天剂量组相比，需要≥2000 mg/天LCIG的患者发生不良事件/药物不良反应（AE/ADR）的发生率更高，包括多发性神经病；“关”期改善情况以及因AE导致的停药率在剂量组之间相似，而在GLORIA中因ADR导致的停药率较低。
需要≥2000 mg/天LCIG的患者表现出的安全性与已确立的LCIG安全性/耐受性相当，临床改善情况相似。虽观察到较高的AE发生率，但仍在LCIG可接受范围内。持续给予LCIG对需要非常高剂量左旋多巴的晚期PD患者有益。
