Pahwa Rajesh, Aldred Jason, Gupta Niodita, Terasawa Emi, Garcia-Horton Viviana, Steffen David R, Kandukuri Prasanna L, Chaudhari Vivek S, Jalundhwala Yash J, Bao Yanjun, Kukreja Pavnit, Isaacson Stuart H
University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS, 66160, USA.
Selkirk Neurology, Spokane, WA, USA.
Neurol Ther. 2022 Jun;11(2):711-723. doi: 10.1007/s40120-022-00332-0. Epub 2022 Feb 22.
A clinical trial in advanced Parkinson's disease (APD) has established the superiority of carbidopa/levodopa enteral suspension (CLES) in reducing total patient "off" time (OFF) and increasing total "on" time without troublesome dyskinesia (ON-woTD) over orally administered immediate-release carbidopa/levodopa tablets (IR-CL). However, temporal patterns of these improvements throughout the waking day have not been examined. In this analysis, time to ON-woTD after waking and patterns of motor-symptom control throughout the waking day were compared between CLES and IR-CL.
Post hoc analyses of APD patient-diary data from the phase 3 randomized controlled trial were used to compare changes in time to ON-woTD after waking, motor-symptom control throughout the waking day, occurrence of extreme fluctuations between OFF and "on" with troublesome dyskinesia, and motor-state transitions with CLES versus IR-CL from baseline to week 12.
The sample included 33 CLES-treated and 30 IR-CL-treated patients. Among the CLES group, the percentage of patient days achieving ON-woTD within 30 min of waking was three times higher at week 12 versus baseline (33% vs. 11%, p = 0.0043); no significant change occurred with IR-CL. When the waking day was divided into four 4-h periods, CLES versus IR-CL treatment produced significantly greater reductions in OFF during three periods, and two periods had increased ON-woTD. Fewer CLES-treated patients had extreme fluctuations at week 12 (3% vs. 23%, p = 0.0224) compared to IR-CL-treated patients. From baseline to week 12, CLES-treated patients had greater reductions in the average number of motor-state transitions compared to IR-CL-treated patients (- 1.6, p = 0.0295).
CLES-treated patients experienced a more rapid onset of ON-woTD after waking and greater consistency of ON-woTD throughout their waking day than IR-CL-treated patients.
一项针对晚期帕金森病（APD）的临床试验已证实，与口服速释卡比多巴/左旋多巴片（IR-CL）相比，卡比多巴/左旋多巴肠内悬浮液（CLES）在减少患者总的“关”期时间（OFF）以及增加总的“开”期时间且无麻烦的异动症（ON-woTD）方面具有优势。然而，尚未对整个清醒日期间这些改善的时间模式进行研究。在本分析中，比较了CLES和IR-CL在醒来后达到ON-woTD的时间以及整个清醒日期间运动症状控制的模式。
使用来自3期随机对照试验的APD患者日记数据进行事后分析，以比较从基线到第12周，醒来后达到ON-woTD的时间变化、整个清醒日期间的运动症状控制、伴有麻烦异动症的OFF和“开”期之间极端波动的发生情况以及CLES与IR-CL之间的运动状态转换。
样本包括33例接受CLES治疗的患者和30例接受IR-CL治疗的患者。在CLES组中，第12周时醒来后30分钟内达到ON-woTD的患者天数百分比与基线相比高出三倍（33%对11%，p = 0.0043）；IR-CL组无显著变化。当将清醒日分为四个4小时时间段时，CLES与IR-CL治疗相比，在三个时间段内OFF的减少更为显著，在两个时间段内ON-woTD增加。与接受IR-CL治疗的患者相比，接受CLES治疗的患者在第12周时出现极端波动的情况较少（3%对23%，p = 0.0224）。从基线到第12周，与接受IR-CL治疗的患者相比，接受CLES治疗的患者运动状态转换的平均次数减少幅度更大（-1.6，p = 0.0295）。
与接受IR-CL治疗的患者相比，接受CLES治疗的患者醒来后ON-woTD的起效更快，且在整个清醒日期间ON-woTD的一致性更高。
