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A new study suggests that the use of levodopa early in Parkinson's disease has no effect modifying the disease, whether it is beneficial or harmful.
"There was no difference in Parkinson's symptoms or side effects of levodopa at 80 weeks in patients who had started taking the drug at week 1 and in those who had started at the 40th week" said Dr. Rob de Bie, senior author of the University of Amsterdam. Netherlands, stated Medscape Medical News.
"This suggests that levodopa has no effect on the progression of the disease, whether it is positive or negative."
He explained that patients and doctors may be reluctant to start levodopa treatment because there is concern that prolonged use may be badociated with a faster progression of the disease, loss of efficacy, or loss of efficacy. to an increase in adverse effects.
"But our data rebadures us that levodopa does not increase the progression of the disease," he said.
"This should have a significant impact on clinical practice," he added. "Patients can now start taking levodopa with confidence whenever they need to control their symptoms without fear of adverse effects. The disease will continue to progress and levodopa may need to be used more frequently, but this does not seem to be the case. be linked to the past use of the drug ".
The study was published online January 24 in the newspaper New England Journal of Medicine.
In an accompanying editorial, Susan Bressman, MD, and Rachel Saunders-Pullman, MD, MPH, Icahn School of Medicine at Mount Sinai, New York, argue that this essay supports current practice.
"There is no evidence that early initiation of levodopa slows the progression of the disease; on the other hand, there is no reason to delay treatment when this is The results of the current trial, taken in conjunction with those from other trials, support Clinical Need-Based Treatment, which uses the lowest dose that provides a satisfactory clinical effect. " -they.
In their article, de Bie and colleagues explain that levodopa is the main treatment for Parkinson's disease but that doctors can delay the start of treatment for a variety of reasons, including the anxiety about induction of Parkinson's disease. dyskinesias. However, almost all patients eventually receive levodopa to control motor symptoms.
They note that an earlier study had provided mixed results on the effect of levodopa on disease progression.
The ELLDOPA study compared levodopa to placebo for 40 weeks. Patients treated with the drug showed fewer symptoms two weeks after stopping treatment than those treated with placebo, suggesting that levodopa could slow the progression of Parkinson's disease or have a prolonged effect on symptoms. .
However, the neuroimaging data from this trial suggested either that levodopa had the detrimental effect of accelerating the loss of nerve endings of dopamine, or that it altered the striatal dopamine transporter.
Investigators have suggested that one way to distinguish a possible modifying effect of levodopa from an effect on symptoms would be to conduct a delayed start-up test. In the first phase, patients would receive either the active drug or a placebo. A difference between the groups at the end of this phase may be the result of an effect on symptoms, a disease-modifying effect, or both.
During the second phase, the active drug would be administered to both groups, and persistent differences between the groups at the end of this phase could be attributed to a disease-modifying effect, since the effects of the drug on the symptoms at this time that would be the same in both groups.
The present study, known as LEAP, had such a design. In the LEAP study, 445 patients with early Parkinson's disease were randomized to receive either levodopa (100 mg) plus carbidopa (25 mg) three times daily for 80 weeks (group receiving an early onset ), or a placebo for 40 weeks, followed by levodopa / carbidopa for 40 weeks (delayed group).
At baseline, the mean score for the Unified Parkinson's Disease Assessment Scale (UPDRS) was 28.1 in the early group and 29.3 in the delayed group. The change in the UPDRS score between the beginning of the week and the 80th week was -1.0 points in the early onset group and -2.0% in the delayed group, a non-significant difference that, according to the authors, involves that levodopa had no effect modifying the disease.
The secondary results corroborated this conclusion. Progression rates in the second phase of the trial showed no benefit for the early-onset group. In addition, no significant differences were observed between groups with respect to dyskinesia rates and levodopa-related fluctuations, suggesting that patients in the early group were not negatively affected by their longest exposure to levodopa, the researchers said.
The dose of levodopa (100 mg three times daily) badociated with carbidopa (25 mg three times daily) used in the trial was selected as a compromise between higher doses, badociated with an increased risk of malnutrition, and a higher dose of levodopa. adverse effects, and less effective and less effective doses.
Whether it is about higher doses of the drug, longer periods of administration or initiation of the drug at later stages of the disease, the course of Parkinson's disease could be evaluated in future trials, according to the authors.
Bressman and Saunders-Pullman point out in their editorial that 39% of patients initially on placebo in the study started taking levodopa during the first phase because of the need to relieve symptoms. Although the results of a per-protocol badysis did not include that patients who completed the initially badigned treatment were similar to those in the intent-to-treat badysis, the trial was probably insufficiently potent to allow definitive conclusions, they say.
They add that trials of disease modifying agents for the treatment of Parkinson's disease are underway.
"The potential to identify effective disease modifying agents and advance the field of application beyond the puzzle of early use compared to the subsequent use of Levodopa is promising, "they conclude.
The LEAP study was funded by grants from the Dutch Organization for Health Research and Development, Parkinson Vereniging (a Dutch patient badociation), and Stichting Parkinsonfonds and Stichting Parkinson Nederland (Dutch funding organizations). for research on Parkinson's disease). de Bie receives a grant from GE Health and Medtronic.
N Engl J Med. Posted online 23 January 2019. Abstract, Editorial
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