Objective: PD MED LATER is a large, pragmatic trial aiming to determine which class of drug when added to levodopa provides the most effective control and best quality of life (QoL) for people with PD who develop poorly controlled motor complications.

Background: Indirect comparisons between placebo-controlled trials of adjuvant drug classes suggest that dopamine agonists (DA) and tolcapone are more effective than monoamine oxidase (MAO) B inhibitors and entacapone in reducing off time.¹ But, such between-trial comparisons are potentially unreliable, so direct head-to-head randomised comparisons are required, preferably using patient-rated QoL as the primary outcome.

Method: 485 UK patients with PD and motor complications were randomised between DA and dopamine degradation inhibitor (DDI) therapy (MAOB inhibitor or catechol-O-methyl transferase (COMT) inhibitor). The primary outcome measure was the mobility dimension on the patient-rated Parkinson’s Disease Questionnaire (PDQ-39) QoL scale. Secondary outcomes included other PDQ-39 dimensions, EuroQol (EQ)-5D, institutionalisation, dementia and mortality. Intention-to-treat analyses used repeated measures regression and log-rank methods.

Results: With over 10 years of follow up, there were no significant differences between DA and DDI therapy in any patient-rated QoL measure or in institutionalisation, dementia or mortality.

PDQ-39 mobility scores were, however, 4.8 points (CI 1.3 to 8.3; p = 0.007) better with MAOB inhibitor than COMT inhibitor (entacapone being used for almost all). There were also borderline significant differences on the PDQ-39 activities of daily living, emotional well-being and social support dimensions together with the summary index (all favouring MAOB inhibitor). A similar trend was observed for EQ-5D. There was no difference between MAOB and COMT inhibitors in rates of institutionalisation, dementia or mortality. In exploratory analyses, similar magnitude differences were seen favouring DA over COMT-inhibitor but these did not reach statistical significance.

Conclusion: There was no difference in patient-rated QoL between DA and DDI therapy. However, QoL was somewhat better in patients receiving MAOB or DA than COMT inhibitors.

References: Stowe R, Ives N, Clarke CE, Handley K, Furmston A, Deane K, et al. Meta-analysis of the comparative efficacy and safety of adjuvant treatment to levodopa in later Parkinson’s disease. Movement Disorders 2011;26:587-98. https://doi.org/10.1002/mds.23517

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MDS Abstracts - https://www.mdsabstracts.org/abstract/long-term-effectiveness-of-adjuvant-treatment-with-catechol-o-methyltransferase-or-monoamine-oxidase-b-inhibitors-compared-with-dopamine-agonists-in-parkinsons-disease-uncontrolled-by-levodop/