MAO-B Inhibitors May Be Underused for Parkinson Disease, Outperform COMT Inhibitors in Quality of Life

Although both are dopamine reuptake inhibitors, those on MAO-B inhibitors demonstrated greater mean PDQ-39 mobility scores and EuroQol 5-dimension 3-level scores over a median of 4.5 years.

Data from the PD MED study (EU Trials: 2005-001813-16) showed that lower 39-item Parkinson’s Disease Questionnaire (PDQ-39) scores and worse long-term motor outcomes occurred for patients with Parkinson disease (PD) who took catechol-O-methyltransferase (COMT) inhibitors as an adjunctive treatment compared with those on monoamine oxidase type B (MAO-B) inhibitors or dopamine agonists.

Findings also showed a slightly worse patient-rated quality of life on MAO-B inhibitors compared with dopamine agonists, although the differences were not significant. These medications did, however, produce equivalent disease control, with the study authors concluding that MAO-B inhibitors may be underused as an adjuvant therapy.

Led by Richard Gray, MSc, Emeritus Professor, University of Oxford, the analysis included 500 patients with idiopathic PD who developed uncontrolled motor complications and were randomly assigned 1:1:1 to either a dopamine agonist (n = 134) or a dopamine reuptake inhibitor (DRI), with the latter group including those on a MAO-B inhibitor (n = 146) or a COMT inhibitor (n = 145). Patients included in the analysis did not have dementia and received these treatments as adjunctive to levodopa therapy to treat their motor complications.

Patients were recruited between February 2001 and December 2009, with data analyzed between 2017 and 2020. The primary end point was change in PDQ-39 mobility scores. Outcomes were assessed before study entry, at 6 and 12 months after randomization, and annually thereafter. After a median of 4.5 years (range, 0-13 years) of follow-up, PDQ-39 mobility scores were a mean of 2.4 points (95% CI, –1.3 to 6.0 points) better for those in the dopamine agonist group compared with the combined MAO-B and COMT groups; however, this difference was not significant (P = .20).

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With regard to solely DRIs, there was a significant mean difference of 4.2 points (95% CI, 0.4-7.9 points; P = .03) in PDQ-39 mobility scores in favor of MAO-B inhibitors compared with COMT inhibitors. Furthermore, these patients also demonstrated more favorable PDQ-39 summary index scores (mean difference, 2.2 points [95% CI, –0.2 to 4.5 points]; P = .07), as well as reached statistical significance on several other PDQ-39 domains, including activities of daily living (mean difference, 4.0 points [95% CI, 0.4-7.5 points]; P = .03) emotional well-being (mean difference, 4.4 points [95% CI, 1.1-7.6 points]; P = .009), and social support (mean difference, 3.7 points [95% CI, 0.8-6.6 points]; P = .01).

Gray and colleagues wrote that "of the 2 DRIs, MAO-B inhibitors were superior to COMT inhibitors for both the PDQ-39 mobility score and the EQ-5D-3L utility score,” noting that the effect size for the PDQ-39 mobility scores was similar to what is considered the minimal clinically important difference of 3.2-points. "Dopamine agonists also outperformed COMT inhibitors by a similar margin but, perhaps because fewer participants were randomized in this comparison, the difference was not significant."

"Although the differences between drug classes in our direct randomized comparisons were not highly significant, they were made more plausible because of the consistency of benefits observed across the different outcome measures” Gray et al. wrote. "The results were also consistent with indirect comparisons between placebo-controlled clinical trials, which suggested that entacapone, the only COMT inhibitor assessed in the PD MED study, was a relatively weak adjuvant agent compared with dopamine agonists and MAO-B inhibitors with regard to off time and levodopa dose reduction."

Over time, patients on MAO-B inhibitors demonstrated significantly increased EuroQol 5-dimension 3-level scores (slopes diverging at a rate of 0.02 points per year [95% CI, 0.001-0.04] in favor of the MAO-B group) compared to those on COMTs. Additionally, these patients had a lower rate of dementia onset (MAO-B: 32% vs COMT: 37%) and lower morality rate (MAO-B: 55% vs COMT: 63%; risk ratio, 0.76 [95% CI, 0.56-1.03]; P = .07).

In exploratory analyses restricted to patients randomized to either dopamine agonists or MAO-B inhibitors, no differences were observed in PDQ-39 scores in either the mobility domain (mean difference, 0.2 points [95% CI, –4.9 to 5.3 points]; P = .93) or the summary index (mean difference, 0.1 points [95% CI, –3.3 to 3.6 points]; P = .94). Investigators observed a mean of 3.4 points (95% CI, –0.7 to 7.6 points) favoring the dopamine agonists when compared only against COMT inhibitors, however, this difference was not significant (P = .10).

Of the 469 patients in the HES database that had information on hospitalizations, 341 (72.7%) were admitted during the study period, with a similar number of recorded nonelective admissions between the MAO-B (mean per patient, 2.25 [standard deviation (SD), 2.99]) and COMT (mean per patient, 2.34 [SD, 2.71]; P = .96). Admission duration between the 2 groups was also similar between those on MAO-B inhibitors (mean, 14.2 [SD, 20.9] days) compared with COMT (mean, 14.3 [SD, 21.2] days; P = .98).

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