Levodopa-Carbidopa Intestinal Gel in Parkinson's Disease: A Systematic Review and Meta-Analysis

Abstract

Background: Levodopa has been widely used and regarded as the most effective therapy for Parkinson's disease (PD), but long-term treatment with oral levodopa may result in motor fluctuations and involuntary movements (dyskinesias). There is evidence to suggest that Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) can effectively manage motor and non-motor complications in PD, but clinical studies investigating this have yielded inconsistent results. This systematic review and meta-analysis was performed to examine the efficacy and safety of LCIG for patients with PD. Methods: A systematic search was conducted to retrieve published data in the EMBASE, PubMed, and the Cochrane Library up to March 2018. Both efficiency and safety of LCIG were analyzed using pooled standardized mean differences (SMDs) or odds ratio (ORs) with 95% confidence interval (CIs). Results: Eight trials with 384 PD patients were included in the present study. Compared with the control group, LCIG significantly decreased off-time (SMD, -1.19; 95% CI, -2.25 to -0.12; p = 0.003) and increased on-time without troublesome dyskinesia (SMD, 0.55; 95% CI, 0.20 to 0.90; p = 0.002). However, no significant difference of LCIG was found in on-time with troublesome dyskinesia. There were no significant differences in UPDRS, Hoehn & Yahr and PDQ-39 scores. Besides, no significant differences in the drop-out and adverse effects. Conclusions: Continuous delivery of LCIG may offer a promising option for PD patients. More randomized double-blind controlled studies with large sample sizes were needed to further confirm the efficacy and safety of LCIG for PD patients.

Keywords: Parkinson's disease; efficacy; levodopa-carbidopa intestinal gel; meta-analysis; safety.

Figure 1

PRISMA flow chart of Study Selection in Meta-analysis.

Figure 2

Forest plots of pooled on-time and off-time in PD patients. Plot A (A), on-time with troublesome dyskinesia, h per day; plot B (B), on-time without troublesome dyskinesia, h per day; plot C (C), off-time, h per day. PD, Parkinson's disease; LCIG, levodopa-carbidopa intestinal gel.

Figure 3

Forest plots of pooled UPDRS scores in PD patients. Plot A (A), UPDRS total scores; plot B (B), UPDRS part II; plot C (C), UPDRS part III. PD, Parkinson's disease; LCIG, levodopa-carbidopa intestinal gel.

Figure 4

Forest plots of pooled PDQ-39 and Hoehn & Yahr scores in PD patients. Plot A (A), PDQ-39 scores; plot B (B), Hoehn & Yahr scores. PD, Parkinson's disease; LCIG, levodopa-carbidopa intestinal gel; PDQ-39, Unified Parkinson's Disease Rating Scale.

Figure 5

Forest plots of pooled withdrawal in PD patients. Plot A (A), withdrawal for any reason; plot B (B), withdrawal for AEs. PD, Parkinson's disease; AEs, adverse effects; LCIG, levodopa-carbidopa intestinal gel.

Figure 6

Forest plots of pooled AE in PD patients. Plot A (A), at least one AE; plot B (B), serious AE. PD, Parkinson's disease; LCIG, levodopa-carbidopa intestinal gel; AE, adverse effect.

Figure 7

Funnel plot of comparison for at least one AE. The funnel plot appeared asymmetric. Each small circle represents an independent study for the indicated association. AE, adverse effects.