Levodopa for Early Parkinson Disease: Some Answers, More Questions

February 26, 2019

Does early initiation of levodopa delay disease progression? Dutch researchers sought to confirm a neuroprotective effect suggested by a previous trial.

RESEARCH UPDATE

A new study suggests that early use of levodopa for treating Parkinson disease (PD) has neither disease-modifying properties, nor is it detrimental to disease course. The results answer some questions but raise others about the role of levodopa in PD.

The study was recently published in the New England Journal of Medicine.1

“We conclude that treatment with levodopa at a dose of 100 mg three times per day in combination with carbidopa at a dose of 25 mg three times per day had no disease-modifying effect, either beneficial or detrimental, on early Parkinson’s disease among patients who were evaluated over the course of 80 weeks,” wrote first author Constant V. M. Verschuur, MD, of the University of Amsterdam, and colleagues with the Levodopa in Early Parkinson’s Disease (LEAP) Study Group.

Levodopa is usually reserved for treatment of motor symptoms later in the course of PD. Experts have long assumed that the drug only treats the symptoms and does not actually improve the underlying disease process.

However, results from the Earlier vs Later L-DOPA (ELLDOPA) study suggested that levodopa may also have disease-modifying properties. Somewhat confusingly, results from that trial suggested that levodopa may also have detrimental effects on the underlying pathophysiology of PD.2

To get to the bottom of things, researchers conducted a double-blind, placebo-controlled, delayed-start trial at seven academic medical centers in The Netherlands. The study included 445 adults with early PD diagnosed within the past 2 years. Researchers randomized 222 participants to levodopa (100 mg three times daily) plus carbidopa (25 mg three times daily) for 80 weeks (early-start group), and 223 participants to placebo for 40 weeks followed by levodopa plus carbidopa for 40 weeks (delayed-start group).

Results and take-home points >

Results

Using the Unified Parkinson’s Disease Rating Scale (UPDRS), the gold standard of PD assessment, researchers found no significant difference between the two groups in terms of worsening of disease severity over the course of the study (difference, 1.0 point; 95% confidence interval, −1.5 to 3.5; P=.44).

Furthermore, the rate of symptom progression did not significantly differ between the two groups, nor did the rates of dyskinesia and levodopa-related fluctuations in motor response (“on-off effects”).

The authors noted that some questions still remain, so more research is needed on the issue. “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,” they concluded.

Take-home points

• Multi-center double-blind, placebo-controlled, delayed-start trial in The Netherlands found no significant difference in worsening of disease severity for early- versus delayed-start levodopa in patients with early PD

• Rate of symptom progression, dyskinesia, and on-off effects did not differ between the two groups

• Results suggest early use of levodopa does not have disease-modifying effects nor is it detrimental to the course of PD

References:

1. Verschuur CVM, Suwijn SR, Boel JA, et al. Randomized delayed-start trial of levodopa in Parkinson’s disease. N Engl J Med. 2019;380:315-324. doi: 10.1056/NEJMoa1809983

2. Fahn S, Oakes D, Shoulson I, et al. Levodopa and the progression of Parkinson’s disease. N Engl J Med. 2004;351:2498-2508.