Levodopa-Carbidopa Intestinal Gel Reduces Dyskinesia in Parkinson's Disease in a Randomized Trial

Eric Freire-Alvarez, Egon Kurča, Lydia Lopez Manzanares, Eero Pekkonen, Cleanthe Spanaki, Paola Vanni, Yang Liu, Olga Sánchez-Soliño, Luigi M Barbato, Eric Freire-Alvarez, Egon Kurča, Lydia Lopez Manzanares, Eero Pekkonen, Cleanthe Spanaki, Paola Vanni, Yang Liu, Olga Sánchez-Soliño, Luigi M Barbato

Abstract

Background: There are limited data regarding the effectiveness of levodopa-carbidopa intestinal gel (LCIG) for dyskinesia.

Objective: Compare the effectiveness of LCIG versus oral optimized medical treatment (OMT) for dyskinesia in patients with advanced Parkinson's disease (PD) using the Unified Dyskinesia Rating Scale (UDysRS).

Methods: This phase 3b, open-label, multicenter, 12-week, interventional study (NCT02799381) randomized 63 LCIG naïve patients with advanced PD (UDysRS ≥30) to LCIG (N = 30) or OMT (N = 33) treatment. Dyskinesia impact was assessed at baseline through week 12 using the UDysRS. PD-related motor and non-motor symptoms, and quality of life (QoL) were also assessed.

Results: Dyskinesias measured by UDysRS were significantly reduced in the LCIG group (n = 24; -17.37 ± 2.79) compared with the OMT group (n = 26; -2.33 ± 2.56) after 12 weeks (-15.05 ± 3.20; 95% CI, -21.47 to -8.63; P < 0.0001). At week 12, LCIG versus OMT also demonstrated significant improvements in "On" time without troublesome dyskinesia (P = 0.0001), QoL (P < 0.0001), global impression of change (P < 0.0001), activities of daily living (P = 0.0006), and Unified Parkinson's Disease Rating Scale (UPDRS) Part III (P = 0.0762). Treatment-emergent adverse events were reported in 27 (44.3%) patients (LCIG, 18 [64.3%]; OMT, 9 [27.3%]). Serious adverse events occurred in 2 (7.1%) LCIG-treated patients.

Conclusions: LCIG significantly reduced dyskinesia compared with OMT. LCIG showed efficacy for treatment of troublesome dyskinesia in patients with advanced PD while demonstrating benefits in both motor and non-motor symptoms and QoL. © 2021 AbbVie Inc. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Keywords: DYSCOVER; dyskinesia; levodopa-carbidopa intestinal gel; optimized medical treatment.

Conflict of interest statement

E. Freire‐Alvarez has received advisory, consulting, and lecture fees from AbbVie Inc., Almirall, Bial, Eisai, UCB Pharma, Teva, and Zambon, and is an investigator on the DYSCOVER study.

E. Kurča was a study investigator.

L. Lopez Manzanares has been compensated for advisory services and has received consulting, research grant support, or speaker honoraria from AbbVie, Acorda, Bial, Intec Pharma, Italfarmaco, Pfizer, Roche, Teva, UCB Pharma, and Zambon, and is an investigator on the DYSCOVER study.

E. Pekkonen is a member of the AbbVie advisory board, a consulting neurologist for Finnish Patient Insurance Centre, chairman of the board for Current Care in Parkinson's Disease of Finland, a member of the Finnish Medical Society and Duodecim, a member of the MDS Non‐Motor Parkinson's Disease Study Group, and is an investigator on the DYSCOVER study. He has received consulting fees from AbbVie, NordicInfu Care AB, and Zambon; lecture fees from Abbott, AbbVie, Medtronic, and Orion; and travel support from Abbott, AbbVie, Boston Scientific, and Medtronic.

C. Spanaki has received honoraria for lecturing, advisory fees, educational grants, and travel grants from AbbVie, Biogen, UCB Pharma Medtronic, Merck Serono, Novartis, Actelion, and Teva, and is an investigator on the DYSCOVER study.

P. Vanni declares no conflicts.

Y. Liu, O. Sánchez‐Soliño, and L. Barbato are employees of AbbVie and may hold AbbVie stock and/or stock options.

© 2021 AbbVie Inc. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Figures

FIG. 1
FIG. 1
Unified Dyskinesia Rating Scale total scores. LS mean change from baseline in UDysRS total scores in the OMT and LCIG treatment groups. The UDysRS total score ranges from 0 to 104 with a lower score indicating less dyskinesia. Asterisks indicate statistical significance compared with baseline in a mixed‐effects model repeated measures at the P < 0.0001 (***) level. Error bars represent SE. BL, baseline; CI, confidence interval; LCIG, levodopa‐carbidopa intestinal gel; LS, least squares; MMRM, mixed‐effect model repeated measures; OMT, optimized medical treatment; SE, standard error; UDysRS, Unified Dyskinesia Rating Scale.
FIG. 2
FIG. 2
Key secondary outcomes. LS mean change from baseline of daily hours of (A) normalized “On” time without troublesome dyskinesia, (B) PDQ‐8 summary index scores, (C) CGI‐C scores, (D) UPDRS II, (E) normalized “Off” time, and (F) UPDRS III. Error bars represent SE. Asterisks indicate statistical significance compared with baseline in a P < 0.05 (*), P < 0.01 (**), and P < 0.001 (***). BL, baseline; CI, confidence interval; LCIG, levodopa‐carbidopa intestinal gel; LS, least squares; MMRM, mixed‐effect model repeated measures; OMT, optimized medical treatment; PDQ‐8, Parkinson's Disease Questionnaire‐8; SE, standard error; UPDRS, Unified Parkinson's Disease Rating Scale.

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