Effects of Levodopa-Carbidopa Intestinal Gel on Dyskinesia and Non-Motor Symptoms Including Sleep: Results from a Meta-Analysis with 24-Month Follow-Up

Abstract

Background: In advanced Parkinson's disease (PD), dyskinesias and non-motor symptoms such as sleep dysfunction can significantly impair quality of life, and high-quality management is an unmet need. Objective: To analyze changes in dyskinesia and non-motor symptoms (including sleep) among studies with levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. Methods: A comprehensive literature review identified relevant studies examining LCIG efficacy. Outcomes of interest were dyskinesia (UDysRS, UPDRS IV item 32), overall non-motor symptoms (NMSS), mentation/behavior/mood (UPDRS I), and sleep/daytime sleepiness (PDSS-2, ESS). The pooled mean (95% confidence interval) change from baseline per outcome was estimated for each 3-month interval with sufficient data (i.e., reported by≥3 studies) up to 24 months using a random-effects model. Results: Seventeen open-label studies evaluating 1243 patients with advanced PD were included. All outcomes of interest with sufficient data for meta-analysis showed statistically significant improvement within 6 months of starting LCIG. There were statistically significant improvements in dyskinesia duration as measured by UPDRS IV item 32 at 6 months (-1.10 [-1.69, -0.51] h/day) and 12 months (-1.35 [-2.07, -0.62] h/day). There were statistically and clinically significant improvements in non-motor symptoms as measured by NMSS scores at 3 months (-28.71 [-40.26, -17.15] points). Significant reduction of NMSS burden was maintained through 24 months (-17.61 [-21.52, -13.70] points). UPDRS I scores significantly improved at 3 months (-0.39 [-0.55, -0.22] points). Clinically significant improvements in PDSS-2 and ESS scores were observed at 6 and 12 months in individual studies. Conclusion: Patients with advanced PD receiving LCIG showed significant sustained improvements in the burden of dyskinesia and non-motor symptoms up to 24 months after initiation.