Early levodopa treatment not justified in Parkinson’s disease
medwireNews: Levodopa does not modify Parkinson’s disease, show study findings suggesting there is no benefit to starting the drug early in the disease course.
The LEAP – Levodopa in Early Parkinson’s Disease – study compared the change in Unified Parkinson’s Disease Rating Scale (UPDS) score between 222 Parkinson’s disease patients randomly assigned to receive levodopa (100 mg three times per day) plus carbidopa (25 mg three times per day) for 80 weeks and 223 assigned to receive placebo for 40 weeks followed by levodopa plus carbidopa for the remaining 40 weeks.
The patients all had early Parkinson’s disease and had insufficient disability to warrant treatment with antiparkinson medication.
The two groups had comparable UPDS scores at baseline, at 28.1 for the early-start group and 29.3 for the delayed-start group, and there was no significant difference in the reduction in score from baseline to week 80, at a respective 1.0 and 2.0 points.
“These findings imply that levodopa had no disease-modifying effect on Parkinson’s disease over the period of the trial”, write Rob de Bie (University of Amsterdam, the Netherlands) and co-researchers in The New England Journal of Medicine.
Supporting the main finding, the researchers found no significant difference in the rate of symptom progression between weeks 4 and 40 and weeks 44 and 80, with an average difference in weekly UPDS scores of just 0.02 points and 0.07 points, respectively.
The difference in the rate of disease progression between weeks 44 and 80 fell short of the prespecified noninferiority margin for early versus delayed receipt of levodopa, of 0.055 points.
Nausea was more common among patients in the early-start group, but otherwise there was no difference in other adverse effects such as dyskinesias and levodopa-related motor fluctuations.
In a related editorial, Susan Bressman and Rachel Saunders-Pullman, from the Icahn School of Medicine, Mount Sinai, New York, USA, say the trial supports current practice.
“There is no evidence that early initiation of levodopa slows progression of the disease; on the other hand, there is no reason to delay therapy when it is clinically indicated”, they comment.
“The results of the current trial, taken together with those of other trials, support treatment that is guided by clinical need and that uses the lowest dose that provides a satisfactory clinical effect.”
However, the editorialists also point out a limitation of the study, noting that 39% of the patients in the delayed-start group needed symptom relief during the first placebo phase of the study and therefore received levodopa before the 40 weeks.
“This finding limits the power of the comparison between the groups in assessing the effect of disease modification”, they explain.
And while a per-protocol analysis that included only those patients who completed their assigned treatment did not support early levodopa treatment for slowing disease progression, Bressman and Saunders-Pullman say “the trial was probably insufficiently powered to allow firm conclusions.”
By Lucy Piper
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