Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson’s Disease: Observations and Dilemmas after 10 Years of Real-Life Experience

Abstract

Advanced Parkinson’s disease (APD) cannot be treated efficiently using the classical medications however, in recent decades invasive therapeutical methods were implemented and confirmed as effective. One of these methods makes it possible to continue the levodopa (LD) supplementation as a gel administered directly into the upper intestine. However, there are a number of unanswered questions regarding this method. Therefore, we retrospectively analyzed a 10-year period of selected patients that were treated with levodopa/carbidopa intestinal gel (LCIG). We included all APD patients with motor fluctuations and dyskinesia at presentation. LCIG treatment was started in 150 patients: on average these patients received LD for 10.6 ± 4.4 years with a frequency of 5.2 ± 1.0/day until the introduction of LCIG. The estimated and the real LCIG dose differed significantly (mean: 1309 ± 321 mg vs. 1877 ± 769 mg). The mean duration of LCIG administration was 19.8 ± 3.6 h, but in a number of 62 patients we had to administer it for 24 h, to maximize the therapeutic benefit. A carefully and individually adjusted LCIG treatment improves the quality of life of APD patients, but questions remain unresolved even after treating a large number of patients. It is important to share the ideas and observations based on the real-life experience related to the optimal timing, the appropriate dose and duration of administration of the LCIG.

Levodopa–Carbidopa–Entacapone Intestinal Gel in Advanced Parkinson Disease: A Multicenter Real-Life Experience

“…Our previous analysis suggests that a characteristic of APD management in Romania, before the initiation of available DAT options, is a more frequent usage of different add-on therapeutic options. 24 Similarly, in terms of the last dopaminergic treatment before the evaluation for eligibility for LECIG, the proportion of dopamine agonists was found to be significantly higher (86%) compared with other literature reports.…”

“…17 This trend is also reflected later in our 10-year database analysis: 150 patients initiated onto LCIG therapy had a daily average of 4.73 ± 1.08 hours of off time at baseline (and 2.96 ± 0.84 hours of dyskinesia in 95 cases, out of which 44 patients presented an average of 3.00 ± 0.82 hours of diphasic dyskinesia). 24 The profile of motor complications in the cohort evaluated in this study before LECIG initiation suggests a similarly “advanced” stage of PD with a daily average of 5.7 ± 2.1 hours of off time and 3.1 ± 2.1 hours of moderate dyskinesia in 47 cases (64%), out of which 19 patients (26%) also had severe dyskinesias and 10 patients (14%) had diphasic dyskinesias (Table 2).…”

“…In Romania, clinicians have accumulated significant experience with enteral infusion of levodopa for over a decade. 23,24 The complex, multidisciplinary evaluation of APD patients to establish the suitability for DAT also the testing of the efficiency of LCIG and the selection of the most convenient dosage regimen have been done in every case during continuous hospitalization in tertiary university teaching hospitals. 24,25 The aim of this study was to describe our multicenter experience with APD patients initiated de novo onto LECIG, available since autumn 2021.…”

“…In our previous publications, we highlighted that PD patients in Romania are treated with similar strategies to those used by neurologists in other countries. [35][36][37][38] Due to the fact that add-on therapeutic options available in Romania are comparable to those in other Central-and Eastern-European countries, we believe that this type of analysis will help clinicians identify suitable candidate patients for LECIG treatment.…”

“…23,24 The complex, multidisciplinary evaluation of APD patients to establish the suitability for DAT also the testing of the efficiency of LCIG and the selection of the most convenient dosage regimen have been done in every case during continuous hospitalization in tertiary university teaching hospitals. 24,25 The aim of this study was to describe our multicenter experience with APD patients initiated de novo onto LECIG, available since autumn 2021. All patients in our cohort were transitioning from oral/ transdermal treatments to LECIG and so underwent PEG-J insertion; however, in clinical practice, patients who have been treated previously with LCIG and have an existing PEG-J system can transition to LECIG, if needed, using a connection adapter.…”