Journal Article

Effects of GBA1 Variants in Patients With Parkinson's Disease and Levodopa–Carbidopa Intestinal Gel: A Nation‐Wide, Multicenter, Longitudinal, “Real‐World” Study. The EPIC Study

D'Anna, Martina, Priori, Alberto, Bonvegna, Salvatore, Picillo, Marina, Gozzi, Andrea, Leta, Valentina, Elia, Antonio E., Cerroni, Rocco, Tamburin, Stefano, Andreasi, Nico Golfrè, Leuzzi, Catia, Avenali, Micol, Zibetti, Maurizio, Pontieri, Francesco E., Calandra‐Buonaura, Giovanna, Mascia, Marcello M., Alimonti, Dario, Cereda, Emanuele, Colucci, Fabiana, Avanzino, Laura, Cilia, Roberto, Bagella, Caterina, Oggioni, Gaia D., Percetti, Marco, Quartarone, Angelo, Mazzetti, Samanta, Liccari, Marco, Valente, Enza Maria, Cossu, Giovanni, Sambati, Luisa, Magistrelli, Luca, Braccia, Arianna, Caputo, Elena, Gaudiano, Gianfranco, Devigili, Grazia, Tamma, Filippo, Modugno, Nicola, Eleopra, Roberto, Canesi, Margherita, Solla, Paolo, Zappia, Mario, Ranghetti, Alessandra, Stefani, Alessandro, Invernizzi, Federica, Antenucci, Pietro, Comi, Cristoforo, Barca, Silvia, Pellicano, Clelia, Lena, Francesco, Cavallieri, Francesco, Sessa, Maria, Bonato, Giulia, Arienti, Federica, Sorbera, Chiara, Telese, Roberta, Suppa, Antonio, Marano, Massimo, Ledda, Claudia, Pacchetti, Claudio, Garavaglia, Barbara, Schirinzi, Tommaso, Tessito

2025

Overview

ABSTRACT Background The outcome of levodopa/carbidopa intestinal gel (LCIG) in Parkinson's disease carriers of GBA1 mutations (GBA‐PD) remains uncertain. Objective To evaluate the safety and efficacy of LCIG in a large PD cohort, focusing on GBA1 variants. Methods This multicenter, retrospective, longitudinal “real‐world” study included consecutive patients with advanced PD treated with LCIG at 31 Italian centers; data were collected at baseline, 1‐, 5‐year, and last‐available follow‐up. Results Data from 512 PD patients (59% male, mean age and disease duration at LCIG initiation 67.0 ± 8.0 and 12.9 ± 5.0 years, respectively) were analyzed. GBA1 genotyping was available for 306 patients (60%), of whom 40 (13%) had GBA1 mutations or risk variants. Mean follow‐up on LCIG was 3.9 ± 2.9 years; 5‐year follow‐up data were available for 159 subjects. At baseline, GBA‐PD had a younger age, shorter PD duration, worse cognition, and more hallucinations than noncarriers. At 1‐ and 5‐year follow‐up, LCIG improved motor and non‐motor symptoms, OFF‐time, and dyskinesias in the entire population. In GBA‐PD, MDS‐UPDRS parts I, II, and III scores did not change, while part IV score improved significantly less than in noncarriers; cognition and orthostatic hypotension symptoms worsened more rapidly. Multivariate analysis of predictors for adverse events and LCIG discontinuation found no significant contribution from GBA1 mutation status. Conclusions GBA1 status does not increase the risk of adverse events or LCIG discontinuation. LCIG is a safe option for advanced GBA‐PD, even in patients with cognitive impairment at baseline. However, GBA‐PD experiences lower efficacy on motor disability and complications and faster cognitive decline than noncarriers.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adverse events / Age / Aged / Antiparkinson Agents - administration & dosage / Antiparkinson Agents - therapeutic use / Carbidopa - administration & dosage / Carbidopa - adverse effects / Carbidopa - therapeutic use / Cognition / Cognition & reasoning / Cognitive ability / Drug Combinations / Dyskinesia / Effectiveness / Female / GBA1 / Gels / Genotyping / Glucosylceramidase - genetics / Humans / Hypotension / Intestine / Italy / LCIG / Levodopa / Levodopa - administration & dosage / Levodopa - adverse effects / Levodopa - therapeutic use / levodopa–carbidopa intestinal gel / Longitudinal Studies / Male / Middle Aged / Movement disorders / Multivariate analysis / Mutation / Neurodegenerative diseases / Original / Parkinson Disease - drug therapy / Parkinson Disease - genetics / Parkinson's disease / real world / Retrospective Studies / Signs and symptoms