Amsterdam, The Netherlands—The dopamine precursor levodopa is the primary treatment for Parkinson’s disease, although initiation is sometimes delayed for reasons such as concerns about dyskinesias.

In 2004, in the Earlier versus Later Levodopa Therapy in Parkinson Disease (ELLDOPA) trial, patients with early Parkinson’s disease received levodopa or placebo, and after 40 weeks the trial regimen was stopped. Researchers found that 2 weeks after cessation of the regimen, the condition of the patients who had received levodopa had not deteriorated as much as in the patients who had received placebo. That raised the question of whether levodopa had slowed the progression of Parkinson’s disease or that the drug had had a prolonged effect on symptoms that was interpreted as ameliorating the underlying disease.

Now, a report in the New England Journal of Medicine provides an answer.

In a multicenter, double-blind, placebo-controlled, delayed-start trial, Dutch researchers randomly assigned patients with early Parkinson’s disease to receive levodopa (100 mg three times per day) in combination with carbidopa (25 mg three times per day) for 80 weeks (early-start group) or placebo for 40 weeks followed by levodopa in combination with carbidopa for 40 weeks (delayed-start group).

The study team was looking at the between-group difference in the mean change from baseline to week 80 in the total score on the Unified Parkinson’s Disease Rating Scale (UPDRS), as well as progression of symptoms. Participants were 445 patients randomly assigned to the early-start and delayed-start groups.

Results indicate that the mean (±SD) UPDRS score at baseline was 28.1±11.4 points in the early-start group and 29.3±12.1 points in the delayed-start group, with the change from baseline to week 80 at -1.0±13.1 points and -2.0±13.0 points, respectively (difference, 1.0 point; 95% confidence interval [CI], -1.5 to 3.5; P = .44).

The study team points out that the “finding of no significant between-group difference at week 80 implies that levodopa had no disease-modifying effect.”

The researchers write that, between weeks 4 and 40, the rate of progression of symptoms, as measured in UPDRS points per week, was 0.04±0.23 in the early-start group and 0.06±0.34 in the delayed-start group (difference, -0.02; 95% CI, -0.07 to 0.03). The corresponding rates between weeks 44 and 80 were 0.10±0.25 and 0.03±0.28 (difference, 0.07; two-sided 90% CI, 0.03 to 0.10).

The difference in the rate of progression between weeks 44 and 80 did not meet the criterion for noninferiority of early receipt of levodopa to delayed receipt, the study authors point out, adding that the rates of dyskinesia and levodopa-related fluctuations in motor response did not differ significantly between the two groups.

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