LEAP trial answers question of whether levodopa promotes progression of PD

Movement disorders

By Mardi Chapman

6 Feb 2019

Uncertainty regarding the effect of levodopa on the progression of early Parkinson’s disease has been resolved with a trial showing the drug has no disease-modifying effect  – positive or negative – and should be used as indicated for the management of symptoms.

A trial of an early- versus late-start for levodopa therapy published in the NEJM has found no difference between the groups on the basis of the Unified Parkinson’s Disease Rating Scale (UPDRS).

The LEAP trial compared 222 patients randomised to a combination of levodopa and cardiodopa for 80 weeks with 223 patients on placebo for the first 40 weeks then combination therapy for weeks 41 to 80.

While there was an improvement in the UPDRS in the early-start group compared to the late-start group at 40 weeks – ostensibly reflecting the effect of treatment on disease symptoms – there was no significant difference between the two groups at week 80.

The mean change in the total UPDRS score from baseline to 80 weeks was -1.0 points in the early-start group compared to -2.0 points in the delayed-start group.

“These findings imply that levodopa had no disease-modifying effect on Parkinson’s disease over the period of the trial,” the study authors said.

The doses of levodopa (100 mg three times daily) and carbidopa (25 mg three times daily) were chosen as a compromise between higher doses associated with a greater risk of side effects, and lower, less effective doses.

“Whether higher doses of the drug, longer periods of administration, or initiation of the drug at later stages of the disease could alter the course of Parkinson’s disease warrants evaluation in future trials,” the investigators said.

An editorial, also published in the NEJM, said the results of the trial support 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.”

“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.”

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