PMID- 35876875
OWN - NLM
STAT- MEDLINE
DCOM- 20220914
LR  - 20220914
IS  - 1432-1459 (Electronic)
IS  - 0340-5354 (Print)
IS  - 0340-5354 (Linking)
VI  - 269
IP  - 10
DP  - 2022 Oct
TI  - Long-term safety, discontinuation and mortality in an Italian cohort with 
      advanced Parkinson's disease on levodopa/carbidopa intestinal gel infusion.
PG  - 5606-5614
LID - 10.1007/s00415-022-11269-7 [doi]
AB  - 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.
CI  - (c) 2022. The Author(s).
FAU - Garri, Federica
AU  - Garri F
AUID- ORCID: 0000-0002-3555-3882
AD  - Parkinson and Movement Disorders Unit, Study Center on Neurodegeneration (CESNE), 
      Department of Neuroscience, University of Padua, Padova, Italy. 
      feder.garri@gmail.com.
AD  - Parkinson Institute, ASST G. Pini-CTO, Milan, Italy. feder.garri@gmail.com.
AD  - Fondazione Grigioni per il Morbo di Parkinson, Parkinson, Italy. 
      feder.garri@gmail.com.
FAU - Russo, Francesco Paolo
AU  - Russo FP
AD  - Gastroenterology/Multivisceral Transplant Unit, Department of Surgery, Oncology, 
      and Gastroenterology, Study Center on Neurodegeneration (CESNE), Padova 
      University, Padova, Italy.
FAU - Carrer, Tommaso
AU  - Carrer T
AD  - Parkinson and Movement Disorders Unit, Study Center on Neurodegeneration (CESNE), 
      Department of Neuroscience, University of Padua, Padova, Italy.
FAU - Weis, Luca
AU  - Weis L
AD  - Parkinson and Movement Disorders Unit, Study Center on Neurodegeneration (CESNE), 
      Department of Neuroscience, University of Padua, Padova, Italy.
FAU - Pistonesi, Francesca
AU  - Pistonesi F
AD  - Department of general Psychology, Study Center on Neurodegeneration (CESNE), 
      Padova University, Padova, Italy.
FAU - Mainardi, Michele
AU  - Mainardi M
AD  - Parkinson and Movement Disorders Unit, Study Center on Neurodegeneration (CESNE), 
      Department of Neuroscience, University of Padua, Padova, Italy.
FAU - Sandre, Michele
AU  - Sandre M
AD  - Parkinson and Movement Disorders Unit, Study Center on Neurodegeneration (CESNE), 
      Department of Neuroscience, University of Padua, Padova, Italy.
FAU - Savarino, Edoardo
AU  - Savarino E
AD  - Gastroenterology/Multivisceral Transplant Unit, Department of Surgery, Oncology, 
      and Gastroenterology, Study Center on Neurodegeneration (CESNE), Padova 
      University, Padova, Italy.
FAU - Farinati, Fabio
AU  - Farinati F
AD  - Gastroenterology/Multivisceral Transplant Unit, Department of Surgery, Oncology, 
      and Gastroenterology, Study Center on Neurodegeneration (CESNE), Padova 
      University, Padova, Italy.
FAU - Del Sorbo, Francesca
AU  - Del Sorbo F
AD  - Parkinson Institute, ASST G. Pini-CTO, Milan, Italy.
FAU - Soliveri, Paola
AU  - Soliveri P
AD  - Parkinson Institute, ASST G. Pini-CTO, Milan, Italy.
FAU - Calandrella, Daniela
AU  - Calandrella D
AD  - Fondazione Grigioni per il Morbo di Parkinson, Parkinson, Italy.
FAU - Biundo, Roberta
AU  - Biundo R
AD  - Department of general Psychology, Study Center on Neurodegeneration (CESNE), 
      Padova University, Padova, Italy.
FAU - Carecchio, Miryam
AU  - Carecchio M
AD  - Parkinson and Movement Disorders Unit, Study Center on Neurodegeneration (CESNE), 
      Department of Neuroscience, University of Padua, Padova, Italy.
FAU - Zecchinelli, Anna Lena
AU  - Zecchinelli AL
AD  - Parkinson Institute, ASST G. Pini-CTO, Milan, Italy.
FAU - Pezzoli, Gianni
AU  - Pezzoli G
AD  - Fondazione Grigioni per il Morbo di Parkinson, Parkinson, Italy.
FAU - Antonini, Angelo
AU  - Antonini A
AUID- ORCID: 0000-0003-1040-2807
AD  - Parkinson and Movement Disorders Unit, Study Center on Neurodegeneration (CESNE), 
      Department of Neuroscience, University of Padua, Padova, Italy. 
      angelo.antonini@unipd.it.
LA  - eng
PT  - Journal Article
DEP - 20220725
PL  - Germany
TA  - J Neurol
JT  - Journal of neurology
JID - 0423161
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Drug Combinations)
RN  - 0 (Gels)
RN  - 46627O600J (Levodopa)
RN  - MNX7R8C5VO (Carbidopa)
SB  - IM
EIN - J Neurol. 2022 Aug 20;:. PMID: 35986763
MH  - Antiparkinson Agents/adverse effects
MH  - *Carbidopa
MH  - Drug Combinations
MH  - Gels/therapeutic use
MH  - Humans
MH  - Levodopa/therapeutic use
MH  - *Parkinson Disease/drug therapy
MH  - Retrospective Studies
MH  - Weight Loss
PMC - PMC9309989
OTO - NOTNLM
OT  - Adverse events (AEs)
OT  - Discontinuation
OT  - Levodopa-carbidopa intestinal gel (LCIG)
OT  - Mortality
OT  - Parkinson's disease (PD)
OT  - Weight loss (WL)
COIS- 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.
EDAT- 2022/07/26 06:00
MHDA- 2022/09/15 06:00
PMCR- 2022/07/25
CRDT- 2022/07/25 11:14
PHST- 2022/04/01 00:00 [received]
PHST- 2022/07/04 00:00 [accepted]
PHST- 2022/07/02 00:00 [revised]
PHST- 2022/07/26 06:00 [pubmed]
PHST- 2022/09/15 06:00 [medline]
PHST- 2022/07/25 11:14 [entrez]
PHST- 2022/07/25 00:00 [pmc-release]
AID - 10.1007/s00415-022-11269-7 [pii]
AID - 11269 [pii]
AID - 10.1007/s00415-022-11269-7 [doi]
PST - ppublish
SO  - J Neurol. 2022 Oct;269(10):5606-5614. doi: 10.1007/s00415-022-11269-7. Epub 2022 
      Jul 25.