COMT Inhibitors Yield Inferior QOL Outcomes vs MAO-B Inhibitors for Adjuvant Treatment of Parkinson Disease

Catechol-O-methyltransferase (COMT) inhibitors may be an inferior adjuvant treatment option for patients with Parkinson disease (PD) based on long-term, patient-rated quality of life scores, according to findings published in JAMA Neurology.

“Many people with Parkinson disease (PD) develop motor complications that are uncontrolled by levodopa dose adjustment. Among these patients, it is uncertain which drug class is more effective as adjuvant therapy,” wrote Richard Gray, MSc, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom, and co-researchers on the purpose of the trial.

Dr Gray et al aimed to compare the long-term effects of adding a dopamine agonist or dopamine reuptake inhibitor (DRI)—a monoamine oxidase type B (MAO-B) inhibitor or a COMT inhibitor—with levodopa therapy using patient-rated quality-of-life scores in patients with PD.

A total of 500 patients with idiopathic PD from 64 neurology and geriatric clinics in the UK, Czech Republic, and Russia, were included in this pragmatic semifactorial randomized clinical trial. All participants had uncontrolled motor complications, and no participants had dementia.

Patients were randomized 1:1:1 to receive an open-label dopamine agonist, MAO-B inhibitor, or COMT inhibitor. Primary outcomes were recorded using the 39-item Parkinson’s Disease Questionnaire (PDQ-39) mobility domain and cost-effectiveness. PDQ-39 mobility scores were recorded prior to the study, at 6 and 12 months into the trial after randomization, and annually afterward. The Median follow-up was 4.5 years.

Participants in the dopamine agonist treatment arm had a 2.4 point better mean PDQ-39 mobility score than the MAO-B and COMT treatment arms combined; however, this was not significant.

The MAO-B treatment arm had a 4.2 point higher mean PDQ-39 mobility score when compared to the COMT treatment arm. The MAO-B treatment arm also had higher EuroQol 5-dimension 3-level utility scores.

Results were similar when comparing outcomes from the dopamine agonist treatment arm with MAO-B treatment arm.

“In this study, patient-rated quality of life was inferior when COMT inhibitors were used as adjuvant treatment compared with MAO-B inhibitors or dopamine agonists among people with PD who experienced motor complications that were uncontrolled by levodopa therapy,” Dr Gray et al concluded. “The MAO-B inhibitors produced equivalent disease control, suggesting that these agents may be underused as adjuvant therapy.” —Erin McGuinness

Reference

Gray R, Patel S, Ives N, 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 Neurol. Published online December 28, 2021. doi:10.1001/jamaneurol.2021.4736