Objective: PD MED EARLY is a large, pragmatic trial aiming to determine which class of drug as initial treatment provides the most effective long-term control and best quality of life (QoL) for people with early PD.

Background: For decades, there has been controversy about which class of drug to use as initial treatment for people with PD who are experiencing significant functional disability.

Method: 1593 newly diagnosed UK PD patients were randomised 1:1:1 between levodopa (LD)-sparing therapy (dopamine agonist (DA) or monoamine oxidase (MAOB) inhibitor) or LD alone. The primary outcome was the mobility dimension on the patient-rated Parkinson’s Disease Questionnaire (PDQ-39) QoL scale. Secondary outcomes included other dimensions of PDQ-39, EuroQol (EQ)-5D, motor complications, institutionalisation, dementia and mortality. Analysis was on an intention-to-treat basis using repeated measures, regression and log-rank survival analyses.

Results: Over 15 years of follow-up, PDQ-39 mobility scores averaged 2.4-points (CI 0.6 to 4.3; p = 0.01) better in patients randomised to LD than LD-sparing, who also had significantly better PDQ-39 activities of daily living (ADL) and summary index, and EQ-5D scores. More dyskinesia was reported with LD (70% vs. 63% at 15 years; p = 0.005). There was no evidence of any differences in treatment efficacy between younger and older ages (<70 years vs. ≥70 years) or in those with greater and lesser levels of disability at baseline (H&Y rating 1-1.5 vs. 2-5). Results suggested LD might reduce rates of dementia (HR: 0.84 (95% CI: 0.73 to 0.98), but there was no evidence of any difference in mortality or institutionalisation rates.

There were no differences between DA or MAOB inhibitors in any rating scale, or in institutionalisation, dementia or mortality.

Conclusion: Patient-rated QoL was slightly better in patients receiving LD than LD-sparing therapy, in spite of the small increase in dyskinesia, with benefits maintained through 15 years of follow-up. MAOB inhibitors appeared as effective as DA as LD-sparing therapy.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/15-year-effects-of-initiating-treatment-for-parkinsons-disease-with-dopamine-agonists-or-monoamine-oxidase-b-inhibitors-compared-with-levodopa-final-results-of-pd-med-early-disease-randomisa/