Recent research in Parkinson’s disease (PD) has highlighted the potential therapies of continuous subcutaneous infusions (CSCI) of levodopa/carbidopa (ND0612) and foslevodopa/foscarbidopa (ABBV-951). This systematic review aims to explore their effectiveness and safety for PD.
Methods
Guided by the PRISMA statement, we systematically searched 3 electronic databases: MEDLINE, Embase, and Cochrane Central. We combined quantitative and qualitative data for synthesis and descriptive analysis. Quality assessment and risk of bias were evaluated by ROBINS-1 and Rob-2 criteria.
Results
We included 6 records with a total of 698 patients. CSCI therapies reduced motor symptoms in PD patients with levodopa-related motor fluctuations and clinical improvements. Infusions-site reactions were the main adverse event recorded.
Conclusions
ND0612 and ABBV-951 are promising options for enhancing motor control and quality of life in PD patients. However, further research is needed to assess long-term efficacy, safety, and comparisons with oral levodopa and device-aided treatments.
GelbDJOliverEGilmanS. Diagnostic criteria for Parkinson disease. Arch Neurol. 1999;56(1):33-39. doi:10.1001/archneur.56.1.33
2.
ArmstrongMJOkunMS. Diagnosis and treatment of Parkinson disease. JAMA. 2020;323(6):548-560. doi:10.1001/jama.2019.22360
3.
Warren OlanowCKieburtzKRascolO, et al.Factors predictive of the development of Levodopa-induced dyskinesia and wearing-off in Parkinson’s disease. Mov Disord. 2013;28(8):1064-1071. doi:10.1002/mds.25364
4.
HauserRA. Levodopa: past, present, and future. Eur Neurol. 2009;62(1):1-8. doi:10.1159/000215875
5.
OlanowCWCalabresiPObesoJA. Continuous dopaminergic stimulation as a treatment for Parkinson’s disease: current status and future opportunities. Mov Disord. 2020;35(10):1731-1744. doi:10.1002/mds.28215
6.
FernandezHHBoydJTFungVSC, et al.Long-term safety and efficacy of levodopa-carbidopa intestinal gel in advanced Parkinson’s disease. Mov Disord. 2018;33(6):928-936. doi:10.1002/mds.27338
7.
FasanoAVisanjiNPLiuLWCLangAEPfeifferRF. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol. 2015;14(6):625-639. doi:10.1016/s1474-4422(15)00007-1
8.
EspayAJStocchiFPahwaR, et al.Safety and efficacy of continuous subcutaneous levodopa–carbidopa infusion (ND0612) for Parkinson’s disease with motor fluctuations (BouNDless): a phase 3, randomised, double-blind, double-dummy, multicentre trial. Lancet Neurol. 2024;23:465-476. doi:10.1016/s1474-4422(24)00052-8
9.
SoileauMJAldredJBudurK, et al.Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson’s disease: a randomised, double-blind, active-controlled, phase 3 trial. Lancet Neurol. 2022;21(12):1099-1109. doi:10.1016/s1474-4422(22)00400-8
10.
LeWittPAStocchiFArkadirD, et al.The pharmacokinetics of continuous subcutaneous levodopa/carbidopa infusion: findings from the ND0612 clinical development program. Front Neurol. 2022;13:1036068. doi:10.3389/fneur.2022.1036068
11.
GiladiNGurevichTDjaldettiR, et al.ND0612 (levodopa/carbidopa for subcutaneous infusion) in patients with Parkinson’s disease and motor response fluctuations: a randomized, placebo-controlled phase 2 study. Parkinsonism Relat Disord. 2021;91:139-145. doi:10.1016/j.parkreldis.2021.09.024
12.
FungVSCAldredJArroyoMP, et al.Continuous subcutaneous Foslevodopa/Foscarbidopa infusion for the treatment of motor fluctuations in Parkinson’s Disease: considerations for initiation and maintenance. Clin Park Relat Disord. 2024;10:100239. doi:10.1016/j.prdoa.2024.100239
PageMJMcKenzieJEBossuytPM, et al.The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Br Med J. 2021;372(71):n71. doi:10.1136/bmj.n71
15.
HigginsJPTThomasJChandlerJ, et al., eds. Cochrane Handbook for Systematic Reviews of Interventions. London, UK: Cochrane; 2024. https://www.training.cochrane.org/handbook
16.
GoetzCGTilleyBCShaftmanSR, et al.Movement disorder society-sponsored revision of the unified Parkinson’s disease rating scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008;23(15):2129-2170. doi:10.1002/mds.22340
17.
PetoVJenkinsonCFitzpatrickRGreenhallR. The development and validation of a short measure of functioning and well being for individuals with Parkinson’s disease. Qual Life Res. 1995;4(3):241-248. doi:10.1007/bf02260863
18.
SterneJACSavovićJPageMJ, et al.RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366(1):l4898. doi:10.1136/bmj.l4898
19.
SterneJAHernánMAReevesBC, et al.ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355(355):i4919. doi:10.1136/bmj.i4919
20.
PoeweWStocchiFArkadirD, et al.Subcutaneous levodopa infusion for Parkinson’s disease: 1 ‐year data from the open‐label BeyoND study. Mov Disord. 2021;36(11):2687-2692. doi:10.1002/mds.28758
21.
OlanowCWEspayAJStocchiF, et al.Continuous subcutaneous levodopa delivery for Parkinson’s disease: a randomized study. J Parkinsons Dis. 2021;11(1):177-186. doi:10.3233/JPD-202285
22.
AldredJFreire-ÁlvarezEАВА, et al.Continuous subcutaneous foslevodopa/foscarbidopa in Parkinson’s disease: safety and efficacy results from a 12-month, single-arm, open-label, phase 3 study. Neurol Ther. 2023;12(6):1937-1958. doi:10.1007/s40120-023-00533-1
LuoDWanXLiuJTongT. Optimally estimating the sample mean from the sample size, median, mid-range and/or mid-quartile range. Stat Methods Med Res. 2018;27:1785-1805.
25.
LeWittPAStocchiFArkadirD, et al.The pharmacokinetics of continuous subcutaneous levodopa/carbidopa infusion: findings from the ND0612 clinical development program. Front Neurol. 2022;13:1036068. doi:10.3389/fneur.2022.1036068
26.
OlanowCWObesoJAStocchiF. Continuous dopamine-receptor treatment of Parkinson’s disease: scientific rationale and clinical implications. Lancet Neurol. 2006;5(8):677-687. doi:10.1016/s1474-4422(06)70521-x
27.
KovácsNBergmannLAnca-HerschkovitschM, et al.Outcomes impacting quality of life in advanced Parkinson’s disease patients treated with levodopa-carbidopa intestinal gel. J Parkinsons Dis. 2022;12(3):917-926. doi:10.3233/jpd-212979
28.
SchragAChoudhuryMKaskiDGallagherDA. Why do patients with Parkinson’s disease fall? A cross-sectional analysis of possible causes of falls. NPJ Parkinsons Dis. 2015;1(1):15011. doi:10.1038/npjparkd.2015.11
29.
RizosAMartinez-MartinPOdinP, et al.Characterizing motor and non-motor aspects of early-morning off periods in Parkinson’s disease: an international multicenter study. Parkinsonism Relat Disord. 2014;20(11):1231-1235. doi:10.1016/j.parkreldis.2014.09.013
30.
ChapuisSOuchchaneLMetzOGerbaudLDurifF. Impact of the motor complications of Parkinson’s disease on the quality of life. Mov Disord. 2004;20(2):224-230. doi:10.1002/mds.20279
31.
BhidayasiriRRuizPHenriksenT. Practical management of adverse events related to apomorphine therapy. Parkinsonism Relat Disord. 2016;33:S42-S48. doi:10.1016/j.parkreldis.2016.11.017
32.
FénelonGMahieuxFHuonRZiéglerM. Hallucinations in Parkinson’s disease: prevalence, phenomenology and risk factors. Brain. 2000;123:733-745.
33.
CruseBMorales-BriceñoHChangFCF, et al.24-hour levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson’s disease. NPJ Parkinsons Dis. 2018;4:34.
34.
NyholmDJanssonRWillowsTRemahlIN. Longterm 24-hour duodenal infusion of levodopa: outcome and dose requirements. Neurology. 2005;65(9):1506-1507.
35.
RicciardiLBoveFEspayKJ, et al.24-Hour infusion of levodopa/carbidopa intestinal gel for nocturnal akinesia in advanced Parkinson’s disease. Mov Disord. 2016;31(4):597-598.
FernandezHHOdinPStandaertDG, et al.Healthcare resource utilization and device-aided therapy discussions with eligible patients across the Parkinson’s disease continuum: revelations from the MANAGE-PD validation cohort. Parkinsonism Relat Disord. 2023;116:105514. doi:10.1016/j.parkreldis.2023.105514
38.
GüntherDAntoniniACostaJ, et al.European Academy of neurology/movement disorder society ‐ European section guideline on the treatment of Parkinson’s disease: I. Invasive therapies. 2022;29(9):2580-2595. doi:10.1111/ene.15386
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
