Levodopa as Initial Parkinson Treatment Shows Best Long-Term Prognostic Outcome for Quality of Life


When compared with levodopa-sparing agents, treatment levodopa alone resulted in significantly better patient-rated Parkinson’s Disease Questionnaire activities of daily living and summary index scores.

Carl Clarke, MD, professor of clinical neurology at the University of Birmingham

Carl Clarke, MD

After 15 years of follow-up, findings from the PD MED EARLY trial showed that patient-rated quality of life (QoL) was slightly better in patients who started levodopa (LD) than LD-sparing therapies, in spite of the small increase in dyskinesia. Monoamine oxidase (MAOB) inhibitors appeared as effective as dopamine agonists (DA), with slightly better QoL than catechol-O-methyl transferase (COMT) inhibitors.1,2

These data were part of 2 presentations from the 2023 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held August 27-31 in Copenhagen, Denmark. Led by Carl Clarke, MD, professor of clinical neurology at the University of Birmingham, the first analysis included 1593 newly diagnosed UK-based patients with PD who were randomly assigned 1:1:1 to LD-sparing therapy, either DA or MAOB inhibitor, or LD alone, with the primary outcome of the mobility dimension on the patient-rated Parkinson’s Disease Questionnaire (PDQ-39) QoL scale.

The trial was designed to evaluate which of these drug classes provides the greatest, long-term control and best QoL for patients with early PD. Over 15 years of follow-up, patients randomized to LD alone averaged 2.4-points (CI, 0.6-4.3; P = .01) better than patients on LD-sparing agents. In addition, this group showed significantly better PDQ-39 activities of daily living and summary index, and EuroQol (EQ)-5D scores. At the conclusion of the 15-year follow-up, dyskinesia was reported in 70% of patients on LD vs 63% of those on LD-sparing therapies (P = .005).

Subgroup analyses showed no between-group differences on outcomes based on age (<70 years vs ≥70 years) and level of disability at baseline (Hoehn and Yahr rating, 1-1.5 vs 2-5). Investigators observed findings that suggested a slightly reduced rate of dementia (HR, 0.84; 95% CI, 0.73-0.98), but there was no evidence of any difference in mortality or institutionalization rates.

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The second analysis from the trial focuses specifically on a cohort of patients (n = 485) who were randomized to either DA or dopamine degradation inhibitor (DDI) therapy such as an MAOB inhibitor or COMT inhibitor. Over 10-year follow-up, there were no significant between-group differences between DA and DDI therapy in any patient-rated QoL measure or in institutionalization, dementia, or mortality. Of note, PDQ-39 mobility scores were 4.8-points (CI, 1.3-8.3; P = .007) better with MAOB inhibitors than COMT inhibitors.2

Additional details from the analysis showed borderline significant differences on the PDQ-39 activities of daily living, emotional well-being and social support dimensions together with the summary index favoring MAOB inhibitors. Similar trends were observed for EQ-5D. There were no between-group differences on rates of institutionalization, dementia, or mortality. Exploratory analyses showed similar magnitude differences favoring DA over COMT inhibitors; however, these did not reach statistical significance.

In the original PD MED trial, published in Lancet Neurology in 2014, findings showed small but persistent benefits for patient-rated mobility scores in LD-treated patients over LD-sparing therapy. Between 2000 and 2009, PDQ-39 mobility scores were 1.4-points (95% CI, 0.0-2.9; P = .05) better in patients on MAOB inhibitors compared with those allocated to DA. In total, 28% of patients on DA and 23% of those on MAOB inhibitors discontinued allocated treatment because of adverse events compared with just 2% of those on LD (P <.0001).3

Click here for more coverage of 2023 MDS Congress.

1. Clarke C, Rick C, Patel S, et al. 15-year effects of initiating treatment for Parkinson’s disease with dopamine agonists or monoamine oxidase B inhibitors compared with levodopa: final results of PD MED early disease randomization. Presented at: 2023 MDS Congress; August 27-31; Copenhagen, Denmark. Abstract 41
2. Clarke C, Rick C, Patel S, et al. Long-term effectiveness of adjuvant treatment with catechol-o-methyltransferase or monoamine oxidase B inhibitors compared with dopamine agonists in Parkinson’s disease uncontrolled by levodopa: final results of the PD MED LATER randomized clinical trial. Presented at: 2023 MDS Congress; August 27-31; Copenhagen, Denmark. Abstract 42.
3. MD MED Collaborative Group. Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson’s disease (PD MED): a large, open-label, pragmatic randomized trial. Lancet Neurol. 2014;384(9949):1196-1205. doi:10.1016/S0140-6736(14)60683-8
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