Continuous subcutaneous levodopa and foslevodopa infusion therapy for motor symptoms of Parkinson disease: A systematic review of observational studies.

BACKGROUND

Parkinson disease affects approximately 6.1 million people worldwide. Although levodopa remains the most effective symptomatic therapy, long-term oral treatment commonly leads to motor fluctuations and dyskinesias that impair quality of life. Continuous subcutaneous levodopa infusion therapies have emerged as less-invasive strategies to provide continuous dopaminergic stimulation and reduce motor complications.

METHODS

This systematic review evaluated the efficacy and safety of continuous subcutaneous levodopa infusion therapies, including ND0612 and foslevodopa/foscarbidopa (ABBV-951), in advanced Parkinson disease (APD). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, PubMed, Scopus, Web of Science, and Google Scholar were searched from inception to April 2026. Observational studies assessing continuous subcutaneous levodopa infusion in adults with APD and motor fluctuations were included. Ten studies comprising 867 patients met the inclusion criteria.

RESULTS

Across studies with follow-up up to 36 months, continuous subcutaneous infusion reduced daily OFF time by approximately 2.0 to 3.5 hours and increased ON time without troublesome dyskinesia. Quality of life scores improved by 5.6 to 10.8 points on Parkinson Disease Questionnaire measures. Infusion-site reactions (ISRs) were the most common adverse events, occurring in 42% to 92% of patients, though most were mild to moderate. Severe ISRs leading to discontinuation occurred in 5% to 12% of patients. ABBV-951 demonstrated numerically lower ISR rates than ND0612 in real-world settings. Systemic adverse events were generally comparable to oral levodopa therapy.

CONCLUSION

Observational evidence supports continuous subcutaneous levodopa infusion therapies as effective options for reducing motor fluctuations in APD, with sustained benefits reported up to 36 months. ISRs remain the principal tolerability concern, but severe discontinuation-related events are uncommon. Further comparative and long-term studies are needed to better define safety, efficacy, and real-world applicability across diverse populations.