Subcutaneous Levodopa in Parkinson's Disease: A Systematic Review and Meta‐Analysis

TL;DR

Subcutaneous levodopa infusion reduces OFF-time in Parkinson's patients but increases infusion-related side effects.

Contribution

Demonstrates subcutaneous infusion as a novel method to reduce OFF-time without increasing peak dopamine levels.

Findings

Subcutaneous infusion reduced daily OFF-time by 1.98 hours compared to oral levodopa.

Improved quality of life and sleep scores, though not always clinically significant.

Increased treatment-emergent adverse events, mainly at the infusion site.

Abstract

Many Parkinson's disease patients receiving oral levodopa/carbidopa experience a troublesome wearing off effect. Higher doses to mitigate OFF‐time are limited by adverse effects occurring at peak dopamine levels, particularly dyskinesia. A novel strategy to reduce OFF‐time without increasing peak dopamine levels is the continuous subcutaneous infusion of levodopa/carbidopa, or their prodrug equivalents foslevodopa/foscarbidopa.

Assess whether subcutaneous infusion therapies safely reduce OFF‐time and improve quality of life scores compared to oral levodopa/carbidopa.

We searched MEDLINE, Embase, CENTRAL and ICTRP up to 28th October 2024 for clinical trials comparing subcutaneous infusions of levodopa or foslevodopa to oral levodopa in Parkinson's disease.

Screening of 1114 records identified seven studies in which 725 patients received subcutaneous infusion regimens of levodopa/carbidopa (ND0612) (407 patients) or foslevodopa/foscarbidopa (318 patients). Moderate quality evidence indicated subcutaneous infusion reduced the daily duration of OFF‐time by 1.98 h (p = 0.0004). Moderate quality evidence indicated improvements in health‐related quality of life score PDQ‐39 (p = 0.0003) and sleep score PDSS‐2 (p = 0.02), but an increase in the rate of treatment‐emergent adverse events, mostly related to the infusion site (p = 0.04).

Subcutaneous infusion therapies produce a clinically and statistically significant reduction in the duration of OFF‐time experienced by patients with Parkinson's disease, compared to oral levodopa/carbidopa. Patient experience is improved by a statistically, but not clinically, significant degree. There are increased adverse events, mostly related to the infusion site. Overall, subcutaneous infusion regimens could provide a meaningful alternative for Parkinson's disease patients who experience severe motor fluctuations with existing levodopa formulations.

Figures