Rasagiline as Adjunct to Levodopa for Treatment of Parkinson’s Disease: A Systematic Review and Meta-Analysis

Abstract

Background. Rasagiline is a selective, irreversible monoamine oxidase type B inhibitor used as monotherapy in early Parkinson’s disease and as an adjunct therapy to levodopa in Parkinson’s disease with motor fluctuations. Objectives. This meta-analysis aimed to provide updated evidence on the efficacy for motor and nonmotor symptoms and the safety of rasagiline/levodopa versus levodopa in patients with Parkinson’s disease experiencing motor fluctuations. Methods. A systematic literature search was conducted (January 18-19, 2021) using PubMed, Cochrane Library, EMBASE, Web of Science, and Google Scholar to identify randomized controlled trials comparing rasagiline/levodopa versus placebo/levodopa in patients with Parkinson’s disease experiencing motor fluctuations. Outcomes included change in wearing-off time, Unified Parkinson’s Disease Rating Scale (UPDRS)/Movement Disorder Society-UPDRS (MDS-UPDRS) II and III scores, treatment-emergent adverse events (TEAEs), and Parkinson’s Disease Questionnaire (PDQ-39) summary index score. A random effect model was used to estimate the treatment effects. Results. Six studies were included (1912 patients). Significant improvements in wearing-off time (standardized mean difference [SMD]: −0.50, 95% confidence interval [CI]: –0.92 to –0.09, $p=0.002$ ), levodopa dosage (SMD: −0.18, 95% CI: −0.35 to –0.01, $p=0.041$ ), UPDRS/MDS-UPDRS II (SMD: −0.39, 95% CI: −0.52 to –0.25, $p<0.0001$ ), UPDRS/MDS-UPDRS III (SMD: −0.30, 95% CI: −0.44 to –0.16, $p<0.0001$ ), and PDQ-39 summary index score (SMD: –0.21, 95% CI: –0.37 to –0.04, $p=0.013$ ) were observed with rasagiline/levodopa versus placebo/levodopa. The incidence of TEAEs did not differ between treatments (risk ratio: 1.13, 95% CI: 0.98–1.30, $p=0.093$ ). Conclusions. This meta-analysis further indicated the superiority of rasagiline/levodopa in improving motor and nonmotor symptoms of Parkinson’s disease, with a similar safety profile to that of levodopa in Parkinson’s disease with motor fluctuations.