Continuous subcutaneous infusion therapies in Parkinson's disease: evidence of efficacy and safety

Continuous dopaminergic drug delivery aims to reduce motor fluctuations in Parkinson's disease (PD). While intestinal levodopa infusions are effecacious, they require gastrojejunal tube insertion. In contrast, subcutaneous (SC) infusions are less invasive. The recent introduction of foslevodopa infusion has renewed interest in SC treatments.

We review the current evidence for continuous SC infusion of apomorphine and levodopa-based formulations. Apomorphine has been used clinically for decades. The TOLEDO study, the first randomized, placebo-controlled trial of apomorphine infusion, demonstrated significant reductions in OFF time and increases in ON time without troublesome dyskinesia. Long-term open-label studies confirmed sustained benefits and relatively good neuropsychiatric tolerability, with low rates of impulse control disorders, likely due to its dopamine receptor profile. Foslevodopa/foscarbidopa is the first – and currently the only - levodopa-based SC formulation to have been approved; another has data from randomized trials. These showed similar efficacy to apomorphine in reducing OFF time and improving good ON time. Subcutaneous treatments commonly induce skin reactions, and it is not yet known whether long term tolerability differs between foslevodopa and apomorphine. Subcutaneous apomorphine, foslevodopa and levodopa all offer substantial benefits for patients with motor fluctuations. All can be used around the clock, although this use is standard with foslevodopa. Side effect profiles and contraindications differ but they all share the advantage of being easily reversible. While questions around optimal strategies for 24h treatment and long-term adherence and tolerability remain, SC infusions offer meaningful improvements and should be considered earlier, as soon as fluctuations become difficult to manage orally.