Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL‐PET study

TLDR

Preclinical studies suggest ropinirole, a D2/D3 dopamine agonist, may be neuroprotective in Parkinson’s disease, and a pilot PET study indicated slower loss of striatal dopamine storage versus levodopa. This 2‑year, prospective, randomized, double‑blind multinational trial compared de novo Parkinson’s patients on ropinirole or levodopa, measuring the reduction in putamen 18 F‑dopa uptake (Ki) as the primary outcome, with 162 of 186 randomized patients analyzed. Ropinirole produced a significantly smaller decline in putamen Ki over two years (−13.4 % vs. −20.3 %, p = 0.022), with parametric mapping revealing lesser reductions in the putamen and substantia nigra, indicating slower disease progression compared to levodopa.

Abstract

Abstract Preclinical studies suggest ropinirole (a D2/D3 dopamine agonist) may be neuroprotective in Parkinson's disease (PD), and a pilot clinical study using 18 F‐dopa positron emission tomography (PET) suggested a slower loss of striatal dopamine storage with ropinirole compared with levodopa. This prospective, 2‐year, randomized, double‐blind, multinational study compared the rates of loss of dopamine‐terminal function in de novo patients with clinical and 18 F‐dopa PET evidence of early PD, randomized 1 to 1 to receive either ropinirole or levodopa. The primary outcome measure was reduction in putamen 18 F‐dopa uptake (Ki) between baseline and 2‐year PET. Of 186, 162 randomized patients were eligible for analysis. A blinded, central, region‐of‐interest analysis showed a significantly lower reduction ( p = 0.022) in putamen Ki over 2 years with ropinirole (−13.4%; n = 68) compared with levodopa (−20.3%; n = 59; 95% confidence interval [CI], 0.65–13.06). Statistical parametric mapping localized lesser reductions in 18 F‐dopa uptake in the putamen and substantia nigra with ropinirole. The greatest Ki decrease in each group was in the putamen (ropinirole, −14.1%; levodopa, −22.9%; 95% CI, 4.24–13.3), but the decrease was significantly lower with ropinirole compared with levodopa ( p < 0.001). Ropinirole is associated with slower progression of PD than levodopa as assessed by 18 F‐dopa PET. Ann Neurol 2003