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Observational Study
. 2025 Jan;32(1):e16535.
doi: 10.1111/ene.16535. Epub 2024 Oct 28.

Effectiveness and safety of levodopa-entacapone-carbidopa infusion in Parkinson disease: A real-world data study

Diego Santos-García  1   2   3   4 , Lydia López-Manzanares  5 , Inés Muro  5 , Pablo Lorenzo-Barreto  5 , Elena Casas Peña  5 , Rocío García-Ramos  6 , Tamara Fernández Valle  7 , Carlos Morata-Martínez  8 , Raquel Baviera-Muñoz  8 , Irene Martínez-Torres  8 , María Álvarez-Sauco  9 , Déborah Alonso-Modino  10 , Inés Legarda  11 , María Fuensanta Valero-García  12 , José Andrés Suárez-Muñoz  12 , Juan Carlos Martínez-Castrillo  13 , Ana Belén Perona  14 , Jose María Salom  15 , Esther Cubo  16 , Caridad Valero-Merino  17 , Nuria López-Ariztegui  18 , Pilar Sánchez Alonso  19 , Sabela Novo Ponte  19 , Elisa Gamo González  19 , Raquel Martín García  19 , Raúl Espinosa  20 , Mar Carmona  21 , Cici Esmerali Feliz  22 , Pedro García Ruíz  22 , Teresa Muñoz Ruíz  23 , Beatriz Fernández Rodríguez  23 , Marina Mata  24
Affiliations
Observational Study

Effectiveness and safety of levodopa-entacapone-carbidopa infusion in Parkinson disease: A real-world data study

Diego Santos-García et al. Eur J Neurol. 2025 Jan.

Abstract

Background and purpose: Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is a recently developed device-aided therapy for advanced Parkinson disease (PD) patients. The aim of this study was to report real-world evidence about the effectiveness, tolerability, and safety of LECIG in PD patients.

Methods: A multicenter observational retrospective study of the first patients who initiated LECIG in Spain was performed. All neurologists with an experience of at least two patients treated until 30 March 2024 were invited to participate. Data about effectiveness and safety from the medical records (V0, pre-LECIG; V1, initiation of LECIG; V2, post-LECIG follow-up) with a total of 246 variables were collected.

Results: Seventy-three PD patients (61.6% males, 70.1 ± 9.1 years old) from 21 Spanish centers with a mean disease duration of 14.4 ± 6.3 years (range = 5-31) were included. Twenty-six patients (35.6%) were switched directly from levodopa-carbidopa intestinal gel. The mean exposure to LECIG was 177.3 ± 110.5 days (range = 7-476). The mean daily OFF time decreased from 5.2 ± 3 (pre-LECIG) to 1.9 ± 1.8 (post-LECIG; n = 66, p < 0.0001). Global improvement was observed in >85% of the patients. No significant change was detected in the levodopa equivalent daily dose from V0 to V2. Only 7% received 24-h infusion, and 24.7% required more than one cartridge per day at V2. Thirty-four patients (46.6%) had at least one adverse event related to LECIG and/or the device system. Five patients (6.8%) discontinued LECIG.

Conclusions: LECIG was safe and effective in advanced PD patients.

Keywords: Parkinson disease; effectiveness; infusion; levodopa–entacapone–carbidopa; safety.

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Conflict of interest statement

D.S.‐G. has received honoraria for educational presentations and advisory services from AbbVie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, Italfarmaco, Teva, Archímedes, Esteve, Stada, and Merz, and grants from the Spanish Ministry of Economy and Competitiveness (PI16/01575) cofounded by Instituto de Salud Carlos III (Concesión de subvenciones de Proyectos de Investigación en Salud de la convocatoria 2020 de la Acción Estratégica en Salud 2017–2020 por el proyecto “Progresión No Motora e Impacto en la Calidad de Vida en la Enfermedad de Parkinson”; Concesión de Contrato para la intensificación de la actividad investigadora en el Sistema Nacional de Salud, Convocatoria 2021, Instituto de Salud Carlos III). L.L.‐M. has received compensation for advisory services or consulting, research grant support, or speaker honoraria from AbbVie, Acorda, Bial, Intec Pharma, Italfarmaco, Pfizer, Roche, Teva, UCB, and Zambon. I.M. has received honoraria for lectures with educational purposes and advisory services from AbbVie, Bial, Lundbeck, Zambon, and Stada. P.L.‐B. has received honoraria for educational presentations and advisory services from Zambon and Orion Pharma. E.C.P. has received honoraria for educational presentations and advisory services from Bial. R.G.‐R. has received honoraria and grants for lecturing and advisory services from AbbVie, Zambón, Bial, Merk, and Stada. R.B.‐M. is supported by a Rio Hortega contract (CM22/00099) from Instituto de Salud Carlos III. I.M.‐T. has received honoraria from AbbVie, Bial, Ipsen, Medtronic, Merz, and Pallex for lecturing. M.Á.‐S. has received honoraria for educational presentations and advisory services from AbbVie, UCB Pharma, Zambon, Bial, and Teva. I.L. has received honoraria for educational presentations and advisory services from AbbVie, UCB Pharma, Zambon, Bial, and Teva. M.F.V.‐G. has received honoraria for educational presentations from Bial. J.C.M.‐C. has received research support from Lundbeck, Italfarmaco, Allergan, Zambon, Merz, and AbbVie. He has received speaking honoraria from AbbVie, Bial, Italfarmaco, Lundbeck, Krka, Teva, UCB, Zambon, Allergan, Ipsen, and Merz. A.B.P. has received honoraria from AbbVie, Bial, Stada, and Merz for lecturing. J.M.S. has received speaking and/or advisory honoraria from Italfarmaco, Bial, Zambon, AbbVie, Esteve, Stada, and Italfarmaco. E.C. has received travel grants from AbbVie, Allergan, and Boston Pharmaceuticals and lecturing honoraria from AbbVie and International Parkinson's Disease Movement Disorder Society. C.V.‐M. has received honoraria for educational services from Zambon, AbbVie, and UCB. N.L.‐A. has received compensation for advisory services or consulting, research grant support, or speaker honoraria from AbbVie, Italfarmaco, Stada, Bial, Zambon, UCB, and Lundbeck. P.S.A. has received honoraria for educational presentations and advisory services from AbbVie, UCB Pharma, Lundbeck, Krka, Zambon, Bial, and Teva. S.N.P. has received honoraria for educational presentations from AbbVie, Alter, and Schwabe Pharma Iberica and travel grants from Bial, Zambón, and Esteve. E.G.G. has received honoraria for educational presentations and advisory services by Italfarmaco, Bial, and Health in Code. R.M.G. has received honoraria for educational presentations and advisory services from Almirall. R.E. has received honoraria for educational presentations or advisory services or travel grants from AbbVie, Stada, Orion, Merz, Bial, Italfarmaco, Novartis, Pfizer, and Lundbeck. M.C. has received honoraria from AbbVie, Bial, Esteve, and Italfarmaco for lecturing and from Bial and Stada for consultant/scientific advisory services. C.E.F. has received honoraria for educational presentations from AbbVie, Bial, Steve, Zambom, and Alter. P.G.R. has received personal compensation for consultancy/scientific advisory board participation from Italfarmaco, Britannia, Bial, Stada, and Esteve and speaking honoraria from Italfarmaco, Bial, Stada, and Esteve. M.M. has received honoraria for educational presentations or advisory services from Stada, AbbVie, Orion Pharma, Italfarmaco, Bial, Zambon, and Esteve. None of the other authors has any conflict of interest to disclose.

Figures

FIGURE 1
FIGURE 1
(a) Change in the mean OFF time from V0 to V2 (n = 66, p < 0.0001). (b) Change in the mean Unified Parkinson's Disease Rating Scale Part III conducted during the ON state (UPDRS‐III‐ON) from V0 to V2 (n = 54, p = 0.005). (c) Change in the frequency of percentage of the day in the OFF state from V0 to V2 (n = 67, p < 0.0001). (d) Change in the frequency of percentage of the day with dyskinesia from V0 to V2 (n = 63, p = 0.033). Data are presented in panels a and b as boxplots, with the box representing the median and the two middle quartiles (25%–75%). Probability values were computed using the Wilcoxon signed‐rank test (a and b) and the marginal homogeneity test (c and d). Mild outliers (circles) are data points that are more extreme than Q1–1.5.
FIGURE 2
FIGURE 2
Percentage of patients suffering from different disabling motor symptoms at V2 versus V0. Red symbols, p ≥ 0.05. Green symbols, p < 0.05 (two symbols, p < 0.0001). The marginal homogeneity test was applied. FOG–OFF, freezing of gait during the OFF state; FOG–ON, freezing of gait during the ON state.
FIGURE 3
FIGURE 3
Percentage of patients suffering from different disabling nonmotor symptoms at V2 versus V0. Red symbols, p ≥ 0.05. Green symbols, p < 0.05 (two symbols, p < 0.0001). The marginal homogeneity test was applied. ICB, impulse control behavior.
FIGURE 4
FIGURE 4
(a) Clinical Global Impression of Change (CGI) according to the opinion of the neurologist (n = 69), patient (n = 71), and caregiver (n = 65) at V2 (follow‐up visit). (b) Patients with a direct initiation of levodopa–entacapone–carbidopa intestinal gel (LECIG) appear in light colors, and those who switched from levodopa–carbidopa intestinal gel (LCIG) to LECIG appear in dark colors. Improvement was observed in 94.1%, 88%, and 89.2% of patients according to the opinion collected by the neurologist, own patient and principal caregiver, respectively.
FIGURE 5
FIGURE 5
Levodopa equivalent daily dose (LEDD) at V0, V1, and V2 and morning dose (mL), infusion rate (mL/h), and extra dose at V1 and at V2 in the whole cohort (a) and the subgroup of patients switching from levodopa–carbidopa intestinal gel to levodopa–entacapone–carbidopa intestinal gel (b). ED, extra dose; IR, infusion rate; MD, morning dose.
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