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. 2022 Oct;269(10):5606-5614.
doi: 10.1007/s00415-022-11269-7. Epub 2022 Jul 25.

Long-term safety, discontinuation and mortality in an Italian cohort with advanced Parkinson's disease on levodopa/carbidopa intestinal gel infusion

Federica Garrì  1   2   3 , Francesco Paolo Russo  4 , Tommaso Carrer  5 , Luca Weis  5 , Francesca Pistonesi  6 , Michele Mainardi  5 , Michele Sandre  5 , Edoardo Savarino  4 , Fabio Farinati  4 , Francesca Del Sorbo  7 , Paola Soliveri  7 , Daniela Calandrella  8 , Roberta Biundo  6 , Miryam Carecchio  5 , Anna Lena Zecchinelli  7 , Gianni Pezzoli  8 , Angelo Antonini  9
Affiliations

Long-term safety, discontinuation and mortality in an Italian cohort with advanced Parkinson's disease on levodopa/carbidopa intestinal gel infusion

Federica Garrì et al. J Neurol. 2022 Oct.

Erratum in

Abstract

Introduction: Levodopa/carbidopa intestinal gel (LCIG) is an effective treatment in patients with advanced Parkinson's disease (PD) with consolidated evidence of clinical efficacy. However, only few studies have assessed long-term safety, causes of discontinuation, mortality, and relative predictors.

Methods: We conducted a retrospective analysis of 79 PD patients treated with LCIG between 2005 and 2020 in two Italian Neurological Centers, recording all adverse events (AEs), including weight loss (WL). Kaplan-Meier curve was used to estimate the time to discontinuation and survival. Cox proportional hazard model was employed to identify predictors of discontinuation and mortality, while Pearson's correlation was used to analyze predictors of WL.

Results: The average follow-up was 47.7 ± 40.5 months and the median survival from disease onset was 25 years. There were three cases of polyradiculoneuropathy Guillain-Barre syndrome-like, all occurred in the early years of LCIG treatment. Twenty-five patients died (32%), 18 on LCIG (including one suicide) and seven after discontinuation. The mean WL was 3.62 ± 7.5 kg, which correlated with levodopa dose at baseline (p = 0.002), levodopa equivalent daily dose (LEDD) baseline (p = 0.017) and off-duration (p = 0.0014), but not dyskinesia. Peristomal complications emerged as a negative predictor of discontinuation (p = 0.008).

Conclusions: LCIG has a relatively satisfactory long-term safety profile and efficacy and a relatively low rate of discontinuation. Peristomal complications may represent a predictor of longer duration of therapy. According to the mortality analysis, LCIG patients show a long lifespan. Delaying the initiation of LCIG does not affect the sustainability of LCIG therapy.

Keywords: Adverse events (AEs); Discontinuation; Levodopa-carbidopa intestinal gel (LCIG); Mortality; Parkinson’s disease (PD); Weight loss (WL).

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Conflict of interest statement

Angelo Antonini has received compensation for consultancy and speaker related activities from UCB, Boehringer Ingelheim, Ever Pharma, General Electric, Britannia, AbbVie, Kyowa Kirin, Zambon, Bial, Theravance Biopharma, Jazz Pharmaceuticals, Roche, Medscape; he receives research support from Bial, Lundbeck, Roche, Angelini Pharmaceuticals, Horizon 2020—Grant 825785, Horizon2020 Grant 101016902, Ministry of Education University and Research (MIUR) Grant ARS01_01081, Cariparo Foundation, Movement Disorders Society for NMS Scale validation. He serves as consultant for Boehringer–Ingelheim for legal cases on pathological gambling.

Ethical declaration

The study was conducted in accordance with the Good Clinical Practice and the International Conference on Harmonization guidelines and any applicable national and local regulations. The authors acted in accordance with the Declaration of Helsinki ethical standards.

Figures

Fig. 1
Fig. 1
Kaplan–Meier curve showing cumulative survival probability in LCIG patients. The vertical tick marks denote censored observations. A median time of survival from PD onset of 25 years, (CI 95%: 22-na) is showed
See this image and copyright information in PMC

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