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Introduction: The DYSCOVER study was a phase 3b, open-label, randomized trial (NCT02799381) that evaluated levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) in patients with Parkinson's disease (PD) and a high burden of dyskinesia at baseline (defined as Unified Dyskinesia Rating Scale [UDysRS] total score ≥ 30). At week 12, patients receiving LCIG versus OMT experienced significant improvements in dyskinesia, pain, and health-related outcomes. The objective of this analysis was to examine correlations between dyskinesia, pain, and health-related outcomes in PD., Methods: This post hoc analysis assessed correlations between UDysRS, King's Parkinson's Disease Pain Scale (KPPS), 8-item Parkinson's Disease Questionnaire (PDQ-8), Unified Parkinson's Disease Rating Scale part II, Clinical Global Impression of Severity (CGI-S) or Change (CGI-C), and "On" time without troublesome dyskinesia at baseline and after 12 weeks of LCIG or OMT. Correlations were assessed by Pearson correlation coefficients (categorization: weak, r = 0.20-0.39; moderate, r = 0.40-0.59; strong, r ≥ 0.60)., Results: Among 61 patients, moderate-to-strong positive and significant correlations were observed between UDysRS and KPPS scores (baseline, r = 0.47; week 12 change from baseline [CFB], r = 0.63; all p < 0.001). UDysRS and KPPS scores had moderate-to-strong positive and highly significant correlations with PDQ-8 scores (baseline, r = 0.45 and 0.46, respectively; CFB, r = 0.54 and 0.64, respectively; all p < 0.001). Moderate positive and significant correlations were observed between UDysRS and CGI-S/CGI-C scores (baseline, r = 0.41; CFB, r = 0.47; all p < 0.001)., Conclusions: In patients with high dyskinesia burden, positive correlations were observed between dyskinesia, pain, and health-related quality of life (HRQoL) at baseline. Improvements in dyskinesia and pain were associated with improvements in HRQoL, demonstrating the clinical burden of troublesome dyskinesia., Trial Registration Number: Clinicaltrials.gov identifier NCT02799381., (© 2024. The Author(s).)

Background: As Parkinson's disease (PD) advances, management is challenged by an increasingly variable and inconsistent response to oral dopaminergic therapy, requiring special considerations by the provider. Continuous 24 h/day subcutaneous infusion of foslevodopa/foscarbidopa (LDp/CDp) provides steady dopaminergic stimulation that can reduce symptom fluctuation., Objective: Our aim is to review the initiation, optimization, and maintenance of LDp/CDp therapy, identify possible challenges, and share potential mitigations., Methods: Review available LDp/CDp clinical trial data for practical considerations regarding the management of patients during LDp/CDp therapy initiation, optimization, and maintenance based on investigator clinical trial experience., Results: LDp/CDp initiation, optimization, and maintenance can be done without hospitalization in the clinic setting. Continuous 24 h/day LDp/CDp infusion can offer more precise symptom control than oral medications, showing improvements in motor fluctuations during both daytime and nighttime hours. Challenges include infusion-site adverse events for which early detection and prompt management may be required, as well as systemic adverse events (eg, hallucinations) that may require adjustment of the infusion rate or other interventions. A learning curve should be anticipated with initiation of therapy, and expectation setting with patients and care partners is key to successful initiation and maintenance of therapy., Conclusion: Continuous subcutaneous infusion of LDp/CDp represents a promising therapeutic option for individuals with PD. Individualized dose optimization during both daytime and nighttime hours, coupled with patient education, and early recognition of certain adverse events (plus their appropriate management) are required for the success of this minimally invasive and highly efficacious therapy., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anna Jeong is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Agnita J. W. Boon is a study investigator and has served as an advisory board member for AbbVie Inc., Stada, and Ever Pharma. She has received a research grant from Stichting ParkinsonFonds and the Erasmus Trust Fund. Amy M. Spiegel is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Arjun Tarakad declarations of interest: none. Eric Freire-Alvarez has received advisory, consulting, and lectures fees from AbbVie Inc., Teva, Bial, Zambon, Esteve, UCB, and Neuraxpharm; and is an investigator on studies funded by AbbVie Inc., Neuroderm, Cerevel, Roche, Anavex, Bial, Zambon, Impax, and Irlab. Enrique Urrea-Mendoza has received advisory/consulting fees from: AbbVie Inc., Defeat MSA USA, and Medtronic. Filip Bergquist has received advisory and lecture fees from AbbVie Inc., GKC, and Britannia; and research support in kind from GKC. He is a board member of Arvid Carlsson Research AB and receives salary from the University of Gothenburg and Sahlgrenska University Hospital. Jason Aldred is a member of the faculty of the University of Washington and Washington State University. He is a study investigator and has received honorarium from AbbVie Inc., Allergan (now AbbVie Inc.), Teva, US WorldMeds, Medtronic, and Abbott. He is an investigator in studies sponsored by AbbVie Inc., Biogen, Acadia, Northwestern University, Neuroderm, Massachusetts General Hospital, and AstraZeneca. He is also a scientific advisor for AbbVie Inc. He has a clinical practice through Selkirk Neurology. Jia Jia is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Jorge Zamudio is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Manon Bouchard has received honoraria for consultancy, lectures, and advisory boards from AbbVie Inc., Allergan (now AbbVie Inc.), Merz, Ipsen, Lilly, Novartis, Paladin, Sunovion, and UCB. She is an investigator for AbbVie Inc., ES-therapeutics, Biohaven, and Pfizer. Maurizio F. Facheris is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Michael J. Soileau has received advisory/consulting fees from: AbbVie Inc., Abbott, Mertz Therapeutics, Medtronic, and Supernus. He has received research support from: AbbVie Inc., Cerevel Therapeutics, CND Lifesciences, Praxis Precision Medicine, and Teva. He has served on the speaking bureau for: AbbVie Inc., Amneal Pharmaceuticals, Kyowa Kirin, and Neurocrine Pharmaceuticals. Martha P. Arroyo is a study investigator with Leo Pharma and Allakos, and has received honoraria and consultant fees from AbbVie Inc. and BMS. She has a clinical practice through Lakeside Dermatology. Nahome Fisseha is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Pavnit Kukreja is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Robert A. Hauser serves on a scientific advisory board for Inhibikase and Stoparkinson. He has received consulting fees from AbbVie Inc., Amneal Pharmaceuticals, Avanex, Biogen, BlueRock Therapeutics, Forsee Pharmaceuticals, Global Kinetics, Inhibikase, Jazz Pharmaceuticals, Kyowa Kirin, MDCE Suzhou, MedRhythms, Merck, Merz, Neurocrine, Neuroderm, Ovid Therapeutics, PD Neurotechnology, Pharma Two B, Regenxbio, Revance, Sage Therapeutics, Scion NeuroStim, Stoparkinson, Sunovion, Supernus Pharmaceuticals, Tolmar, Tremor Research Group, Tris Pharma, UCB, and Vivifi Biotech. He has received speaking fees from Acorda, Amneal Pharmaceuticals, Cerevel, Inhibikase, Kyowa Kirin, Neurocrine Biosciences, Sunovion, and Supernus. His University has received research support from AbbVie Inc., Aeon Biopharma, Annovis Bio Inc., Artizan Biosciences, Biogen MA, Bukwang Pharmaceutical Co. Ltd., Cavion Inc., Cerevance Inc., Cerevel Therapeutics, Cynapsus Therapeutics, Enterin Inc., Genetech, Global Kinetics Corporation, Hoffman-La Roche Inc., Impax Laboratories, Inhibikase Therapeutics, Integrative Research Laboratories Sweden, Lundbeck Inc., Michael J. Fox Foundation for Parkinson’s Research, National Parkinson’s Foundation, Neuraly Inc., Neurocrine Biosciences, Neuroderm, Parkinson’s & Movement Disorder Alliance, Pharma Two B Ltd., Revance Therapeutics, Sage Therapeutics, Sanofi Pharmaceuticals, Scion NeuroStim, SunPharma, and UCB BioPharma. He holds stock options in Axial Therapeutics, Enterin, and Inhibikase as well as holds stock in Revance Therapeutics. He has received intellectual property interests from a Parkinson’s Disease Diary through his University. He acknowledges a Center of Excellence grant from the Parkinson Foundation. Rajesh Pahwa serves as a consultant for Abbott, AbbVie Inc., ACADIA, Acorda, Adamas, Amneal, CalaHealth, Global Kinetics, Impel, Neuropharma, Kyowa, Lundbeck, Mitsubishi, Neurocrine, Orbis Bioscience, PhotoPharmics, Prilenia, Sunovion, Teva Neuroscience, and US WorldMeds. He receives research support from Abbott, AbbVie Inc., Addex, Biogen, Biohaven, Boston Scientific, EIP, Global Kinetics, Impax, Intec, Lilly, Neuroderm, Neuraly, Parkinson’s Foundation, Pharma 2B, Prelinia, Roche, SIS, Sun Pharma, Sunovion, Theranexus, Theravance, US WorldMeds, and Voyager. He is also an investigator for AbbVie Inc. Sarah Bray has received advisory fees from AbbVie Inc., receives a salary from NSW Health, and is a Nurse Coordinator on studies funded by AbbVie Inc. Sara Dhanani received advisory honoraria from Amneal and AbbVie Inc., and is an investigator on studies funded by AbbVie Inc. Saritha Talapala is an employee of AbbVie Inc., and may hold AbbVie Inc. stock and/or stock options. Victor S. C. Fung receives a salary from NSW Health; has received unrestricted research grants from the Michael J. Fox Foundation, AbbVie Inc., and Merz; and receives royalties from Health Press Ltd. and Taylor and Francis Group LLC., (© 2024 AbbVie Inc.)

Introduction: Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinson's disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD., Methods: Male and female patients with levodopa-responsive PD and ≥ 2.5 hours of "Off" time/day received 24-hour/day foslevodopa/foscarbidopa CSCI at individually optimized therapeutic doses (approximately 700-4250 mg of LD per 24 hours) for 52 weeks. The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in normalized "Off" and "On" time, percentage of patients reporting morning akinesia, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson's Disease Sleep Scale-2 (PDSS-2), 39-item Parkinson's Disease Questionnaire (PDQ-39), and EuroQol 5-dimension questionnaire (EQ-5D-5L)., Results: Of 244 enrolled patients, 107 discontinued, and 137 completed treatment. Infusion site events were the most common adverse events (AEs). AEs were mostly nonserious (25.8% of patients reported serious AEs) and mild/moderate in severity. At week 52, "On" time without troublesome dyskinesia and "Off" time were improved from baseline (mean [standard deviation (SD)] change in normalized "On" time without troublesome dyskinesia, 3.8 [3.3] hours; normalized "Off" time, -3.5 [3.1] hours). The percentage of patients experiencing morning akinesia dropped from 77.7% at baseline to 27.8% at week 52. Sleep quality (PDSS-2) and quality of life (PDQ-39 and EQ-5D-5L) also improved., Conclusion: Foslevodopa/foscarbidopa has the potential to provide a safe and efficacious, individualized, 24-hour/day, nonsurgical alternative for patients with PD., Trial Registration Number: ClinicalTrials.gov identifier NCT03781167., (© 2023. The Author(s).)

Background: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD)., Objective: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity., Methods: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort fromJanuary 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL:1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8)., Results: Four hundred and thirty-nine PD patients (62.05±7.84 years old; 59% males) were included. MNCD stage was:stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advancedMNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p< 0.0001) and EUROHIS-QOL8 (p< 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages., Conclusion: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD.