A new real world study in a large population with a longer follow-up period provides a robust assessment of the efficacy of concomitant medications in Parkinson's disease not controlled by Levodopa.
While L-dopa therapy usually works well at first, after longer or high-dose regimens, practitioners and patients often struggle with premature diminution of effect, unpredictable changes between on and off phases, and dyskinesia. A recent study published in JAMA Neurology provides comparative real-world data on the efficacy of the most common concomitant medications used to reduce these complications and the dose of Levodopa.1,2
Previous studies mostly examined these types of drugs in comparison with placebo and over relatively short periods of time. For the current study, 500 patients were randomized 1:1:1 to a dopamine agonist or a dopamine reuptake inhibitor (COMT or MAO-B inhibitor) in addition to Levodopa and monitored for an average of 4.5 years.
The patients were drawn from 64 centers across Europe, primarily the United Kingdom, aged 73 years on average, majority male (63%), and suffered from uncontrolled impaired motor function while on Levodopa treatment.
Participants in the dopamine agonist group scored 2.4 points better on average on the PDQ-39 (Parkinson's Disease Questionnaire) mobility scale than did participants in the two cohorts on dopamine reuptake inhibitors (DRIs) combined; however, this difference was not significant. Within the DRI group, participants who were given MAO-B inhibitors scored 4.2 points better than those who were given COMT inhibitors. A comparison of dopamine agonists only with MAO-B inhibitors showed no measurable differences in terms of controlling disease progression.
The authors conclude that in this randomized clinical trial, there was no improvement in patient-reported quality of life for advanced Parkinson's disease with dopamine agonists compared to DRIs (MAO-B or COMT inhibitors). The use of either dopamine agonists or MAO-B inhibitors as initial adjuvant therapy appeared to be preferable over Entacapone, the only COMT inhibitor studied. MAO-B inhibitors provided comparable disease control to dopamine agonists, suggesting that MAO-B inhibitors may be underutilized as adjunctive therapy.
1. Gray, R. et al. Long-term Effectiveness of Adjuvant Treatment With Catechol-O-Methyltransferase or Monoamine Oxidase B Inhibitors Compared With Dopamine Agonists Among Patients With Parkinson Disease Uncontrolled by Levodopa Therapy: The PD MED Randomized Clinical Trial. JAMA Neurology (2021).
2. Use of certain enzyme-blocking drugs found to decrease quality of life in patients with PD.