A Systematic Review and Meta-Analysis of the Efficacy and Safety of Rasagiline or Pramipexole in the Treatment of Early Parkinson's Disease

Abstract

Background: Rasagiline or pramipexole monotherapy has been suggested for the management of early Parkinson's disease (PD). The aim of this research was to systematically review the clinical efficacy and safety of rasagiline or pramipexole in early PD (defined as disease duration ≤5 years and Hoehn and Yahr stage of ≤3).

Methods: Randomized controlled trials (RCTs) of rasagiline or pramipexole for early PD published up to September 2021 were retrieved. Outcomes of interest included changes in the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III and the incidence of adverse events. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated, and heterogeneity was measured with the I² test.

Results: Nine rasagiline and eleven pramipexole RCTs were included. One post hoc analysis of one rasagiline study was included. Five studies for each drug were included in meta-analyses of the UPDRS scores. The rasagiline meta-analysis focused on patients receiving 1 mg/day. Rasagiline and pramipexole significantly improved UPDRS Part II and III scores when compared to placebo. Significant heterogeneity among the studies was present (I² > 70%). Neither rasagiline nor pramipexole increased the relative risk for any adverse events, serious adverse events, or adverse events leading to withdrawal when compared with placebo.

Conclusion: Applying a Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach to summarize the evidence, we found moderate confidence in the body of evidence for the efficacy of rasagiline or pramipexole in early PD, suggesting further well-designed, multicenter comparative RCTs remain needed.

Figure 1

PRISMA flowchart for the literature search process. One included study had both rasagiline and pramipexole as interventions.

Figure 2

Risk of bias table of the included studies. Green, yellow, and red denote low, unclear, and high risk of bias, respectively.

Figure 3

Forest plots of the standardized mean difference in Unified Parkinson's Disease Rating Scale II (UPDRS II (a)) and III (UPDRS III (b)) following the administration of rasagiline at 1 mg/day. Rasagiline improved both UPDRS II and UPDRS scores. Significant heterogeneity was seen in the included studies.

Figure 4

Forest plots of the standardized mean difference in Unified Parkinson's Disease Rating Scale II (UPDRS II (a)) and III (UPDRS III (b)) following the administration of pramipexole. Pramipexole improved both UPDRS II and UPDRS III scores. Significant heterogeneity was seen in the included studies.

Figure 5

Forest plots of the relative risk of developing any adverse event (a), a serious adverse event (b), or an adverse event leading to withdrawal following the administration of rasagiline (c). Treatment with rasagiline did not increase the incidence of adverse events when compared with the use of either a placebo or pramipexole. The included studies were homogeneous.

Figure 6

Forest plots of the relative risk of developing any adverse event (a), a serious adverse event (b), or an adverse event leading to withdrawal following the administration of pramipexole (c). Treatment with pramipexole did not increase the incidence of adverse events when compared with the use of either a placebo. The included studies were homogeneous (a, b) or had moderate heterogeneity (c).