Long-Term Clinical Efficacy, Safety, and Polypharmacy Simplification of Levodopa-Entacapone-Carbidopa Intestinal Gel in Advanced Parkinson's Disease: An 18-Month Longitudinal Study.

Background: Advanced Parkinson's disease (aPD) is characterized by motor fluctuations, unpredictable oral absorption, and severe dyskinesias. Levodopa-entacapone-carbidopa intestinal gel (LECIG) is designed to provide dopaminergic stimulation and optimize levodopa bioavailability. We evaluated 18-month clinical outcomes, motor stabilization, disease burden, and oral medication simplification in a real-world cohort transitioning to LECIG. Methods: This retrospective longitudinal study included 41 patients with medication-refractory aPD. Patients underwent nasojejunal titration (mean 5.58 ± 1.50 days), followed by percutaneous endoscopic gastrojejunostomy. Assessments were performed at baseline, initiation, and 6, 12, and 18 months. Primary endpoints were daily OFF time, dyskinesia duration, and non-linear fluctuations. Disease burden was analyzed using Linear Mixed-Effects Models and medication changes using McNemar tests and paired t-tests. Results: Patients (56.1% male; mean age 65.39 ± 8.32 years; disease duration 10.46 ± 4.23 years) demonstrated significant and sustained clinical improvements. For the 38 patients evaluable at 18 months, daily OFF time decreased from 4.67 ± 0.79 h to 1.34 ± 0.40 at initiation and 1.55 ± 0.69 at 18 months (p < 0.0001; 66.8% reduction). Severe peak-dose dyskinesia was absent after initiation (2.17 ± 1.00 to 0.00 h/day; p < 0.001), whereas early morning akinesia decreased from 78.0% to 36.6% and freezing of gait from 56.1% to 31.6%. Total Clinical Burden Score decreased from 9.33 to 3.49 (-62.6%). Dopamine agonist use decreased from 80.5% to 42.1% at 18 months (McNemar p < 0.0001), while adjunct medications decreased from 1.73 to 1.39/patient (p = 0.0284). Adverse events were predominantly mild-to-moderate. No patient discontinued therapy because of an adverse event or hardware failure; one patient discontinued LECIG by personal choice. Two additional patients died from sudden cardiac arrest during follow-up, both considered unrelated to LECIG therapy or pump hardware. At 18 months, 38 of 41 patients remained evaluable. Conclusions: In this observational cohort, LECIG initiation was followed by sustained reductions in motor complications, OFF time, and clinical burden over 18 months. Treatment was also associated with a reduction in dopamine agonist use and overall adjunctive medication burden. The favorable tolerability and low discontinuation rate observed support further evaluation of LECIG as an advanced treatment pathway. However, pre-switch LEDD calculations may support initial pump programming but should not be considered definitive predictors of individualized maintenance settings; inpatient clinical titration remains necessary.