Objective: To investigate the safety and efficacy of LCIG in PD, focusing on the effects of GBA status.
Background: Parkinson’s disease carriers of GBA mutations/variants (PD-GBA) progress more rapidly with earlier cognitive dysfunction and psychosis.[1] The long-term outcome of STN-DBS in PD-GBA has been questioned,[2,3] increasing interest on the risk-benefit profile of alternative device-aided therapies, including Levodopa-carbidopa intestinal gel (LCIG).
Method: This multicentre, retrospective ‘real-world’ study (n=31 movement disorders units) included PD patients consecutively treated with LCIG. GBA status was defined as carrier, noncarrier, not available. Data were collected prior to LCIG initiation (baseline), after 1 year and at long-term follow-up (5-year and last visit censored up to 10 years). Early dropouts (<1 year) were included.
Results: A total of 512 patients with advanced PD (males 59%, age at LCIG 67.0±8.0 ys, PD duration at LCIG 12.9±5.0 ys) were included, of whom 306 (59.8%) underwent GBA genotyping. Pathogenic variants were detected in 13.1% (40/306). At baseline, GBA-PD had younger age at onset, shorter PD duration at LCIG than noncarriers. MoCA, MMSE, FAB scores were lower in PD-GBA vs. noncarriers, whereas hallucinations and use of antipsychotics were more common in GBA-PD.
At 1-year follow-up, LCIG improved motor fluctuations and dyskinesias (p<0.001), axial complications (posture, FOG, postural instability, recurrent falls), psychosis, ICDs, and pain in the entire cohort of 512 PD, with a concomitant reduction of daily dose of DAs, iMAO-B, iCOMT. LCIG was discontinued in 191 patients (37,3%), after a median of 7 years, of whom 31 before 9 months.
MDS-UPDRS-II and -IV (fluctuations) scores improved significantly less in PD-GBA than noncarriers (test-for-interaction p<0.05). Multivariate analysis on the causes of dropout and adverse events excluded an effect of GBA status. GBA-PD showed more severe worsening of MDS-UPDRS part I and MoCA scores and more frequent orthostatic hypotension than noncarriers.
At long-term follow-up up to 10 years, GBA status was not a predictor of discontinuation (adjusted Cox regression model).
Conclusion: This is the largest cohort of PD with LCIG investigated so far. LCIG is relatively safe and effective in GBA-PD, including those with cognitive decline. Nonetheless, close monitoring is recommended.
References: 1. Cilia R, Tunesi S, Marotta G, et al. Survival and dementia in GBA-associated Parkinson’s disease: The mutation matters. Ann Neurol. 2016;80(5):662-673. doi:10.1002/ana.24777
2. Pal G, Mangone G, Hill EJ, et al. Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in GBA Mutation Carriers. Ann Neurol. 2022;91(3):424-435. doi:10.1002/ana.26302
3. Avenali M, Zangaglia R, Cuconato G, et al. Are patients with GBA-Parkinson disease good candidates for deep brain stimulation? A longitudinal multicentric study on a large Italian cohort. J Neurol Neurosurg Psychiatry. Published online October 25, 2023. doi:10.1136/jnnp-2023-332387.
To cite this abstract in AMA style:
R. Cilia, F. Colucci, E. Cereda, V. Leta, M. Zibetti, M. Carecchio, S. Bonvegna, G. Calandra-Buonaura, R. Cerroni, R. de Micco, S. Tamburin, L. Magistrelli, F. Lena, M. Mascia, M. Picillo, G. Cossu, M. Marano, C. Leuzzi, C. Comi, A. Zampogna, C. Pellicano, S. Barca, V. Fioravanti, A. Pilotto, R. Zangaglia, M. Avenali, C. Sorbera, F. Di Biasio, F. Arienti, A. Nicoletti, C. Bagella, MC. Malaguti, A. Ranghetti, E. Caputo, D. Alimonti, E. Torre, GD. Oggioni, AE. Elia, N. Golfrè Andreasi, G. Devigili, B. Garavaglia, G. Imbalzano, T. Schirinzi, F. Cavallieri, A. Priori, M. Sessa, F. Tamma, M. Canesi, P. Solla, M. Zappia, A. Di Fonzo, L. Avanzino, A. Quartarone, EM. Valente, C. Pacchetti, A. Padovani, F. Valzania, A. Suppa, MT. Pellecchia, N. Modugno, M. Tinazzi, A. Tessitore, A. Stefani, P. Cortelli, IU. Isaias, A. Antonini, MC. Sensi, L. Lopiano, R. Eleopra. Effects of GBA mutations in patients with Parkinson’s disease and Levodopa-carbidopa intestinal gel: a nation-wide longitudinal multicentre ‘real-world’ study. [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/effects-of-gba-mutations-in-patients-with-parkinsons-disease-and-levodopa-carbidopa-intestinal-gel-a-nation-wide-longitudinal-multicentre-real-world-study/. Accessed June 14, 2025.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/effects-of-gba-mutations-in-patients-with-parkinsons-disease-and-levodopa-carbidopa-intestinal-gel-a-nation-wide-longitudinal-multicentre-real-world-study/