Continuous Subcutaneous Foslevodopa/Foscarbidopa Improves Nonmotor Symptoms and Fluctuations in Parkinson's Disease

Nonmotor fluctuations (NMFs) in Parkinson's disease (PD) represent a heterogeneous and disabling feature often linked to pulsatile dopaminergic stimulation from oral levodopa. Continuous subcutaneous foslevodopa/foscarbidopa infusion (CSFLI) provides 24-h levodopa delivery, with established motor benefits but limited real-world data on NMFs. We investigated changes in motor complications, nonmotor symptoms, and NMFs over 3 months after initiation of CSFLI.

In this prospective, single-center, real-world study, 66 patients with advanced PD initiated CSFLI. Longitudinal 3-month data were available for 40 patients. Motor complications were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV, motor severity with UPDRS Part III, and nonmotor symptoms with the Nonmotor Symptom Scale (NMSS); nonmotor fluctuations were evaluated with the Nonmotor Fluctuation Assessment questionnaire (NoMoFa). Additional validated scales assessed sleep, mood, fatigue, autonomic, and behavioral symptoms. Longitudinal changes were analyzed using paired parametric or non-parametric tests, as appropriate, with FDR correction.

After 3 months, motor complications significantly improved, with reductions in OFF time and ON time with dyskinesias. Nonmotor symptom burden also improved, with significant reductions in NoMoFa total and NMF-OFF scores, whereas NMF-ON remained unchanged. Improvements were also observed in sleep-related symptoms, depressive symptoms, and quality of life, whereas apathy, autonomic symptoms, and daytime sleepiness did not significantly change.

CSFLI was associated with improvements in motor complications and nonmotor fluctuations, particularly OFF-related NMFs, together with benefits in specific nonmotor symptoms. These findings provide preliminary real-world evidence supporting a potential role of CSFLI in the management of NMFs in PD.