Objective: We present the results of several post hoc analyses of the LEAP-study.

Background: Among patients with Parkinson’s disease who were evaluated in the LEAP-study [1], treatment with levodopa/carbidopa had no disease-modifying effect.

Method: The LEAP-study is a multicenter, double-blind, placebo-controlled, randomized delayed-start trial. A total of 445 patients were randomized to receive levodopa/carbidopa 300/75 mg per day for 80 weeks (early-start group; n=222) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg per day for 40 weeks (delayed-start group; n=223). We compared the development of motor response fluctuations (three separate questions concerning wearing off) and dyskinesias (UPDRS item 32) at 80 weeks between the two groups, also for several separate age-cohorts. We analyzed the between-group difference in quality of life measured with the Parkinson’s Disease Questionnaire-39 (PDQ-39) for all available time points. Furthermore, we report the response of bradykinesia, tremor, and rigidity to levodopa.

Results: There was a slight between-group difference in early motor response fluctuations favoring the early-start group. There was no statistically significant difference in dyskinesias at 80 weeks, also not for the separate age cohorts (note small sample sizes; under 50 years n=11; 50 to 59 years n=51). The between group difference in median PDQ-39 score is in favor of the early start group at 22 weeks (early-start group median 7.7, IQR=3.2-13.5; delayed-start group median 9.0, IQR=5.1-18.0; p=0.003) and at 40 weeks (early-start group median 7.7, IQR=3.5-15.4; delayed-start group median 10.3, IQR = 5.1-16.4; p=0.043). This increase in quality of life in the early-start group is mainly due to an increase in the ability to perform ADL. After start of levodopa in the delayed-start group at week 40, there is no statistically significant difference in PDQ-39 between the two groups. The symptoms bradykinesia, rigidity and tremor respond at the same degree to a low dose of levodopa.

Conclusion: In this study we did not find that earlier start of levodopa induced more motor response fluctuations and dyskinesias at 80 weeks. Patients with early PD without disability can gain quality of life by a use of a low dose of levodopa.

References: [1] Verschuur CVM, Suwijn SR, Boel JA, et al. Randomized Delayed-Start Trial of Levodopa in Parkinson’s Disease. New Engl J Med 2019; 380:315-24.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-levodopa-in-early-parkinsons-disease-leap-study-post-hoc-analyses/