Indirect Comparison of Ropinirole and Pramipexole as Levodopa Adjunctive Therapy in Advanced Parkinson's Disease: A Systematic Review and Network Meta-Analysis

IntroductionTo evaluate the comparative efficacy and safety of ropinirole and pramipexole as adjunctive therapies to levodopa (l-dopa) for the management of advanced Parkinson's disease (PD), via a systematic review and network meta-analysis.MethodsTwenty-one double-blind randomised controlled trials of patients with advanced PD with motor fluctuations receiving l-dopa comparing ropinirole or pramipexole with comparators were identified from 2550 publications. Bayesian indirect comparison methods were applied to independently review efficacy outcomes including off-time reduction, Unified Parkinson's Disease Rating Scale-Activity of Daily Living (UPDRS-ADL) and UPDRS-motor scores, and safety outcomes including adverse events (AE) and patient withdrawals, to determine indirect treatment comparison mean differences (MD) or hazard ratios (HR) with 95% confidence intervals (CI).ResultsThe indirect efficacy comparison resulted in a statistically nonsignificant off-time reduction difference (hours) of ropinirole-sustained release (SR) versus pramipexole-immediate release (MD -0.25; 95% CI -0.71, 0.21) and ropinirole-SR versus pramipexole-extended release (ER) (MD 0.18; 95% CI -0.40, 0.76). Ropinirole-SR adjunctive treatment showed a tendency towards more improvement in UPDRS-ADL score (MD 1.24; 95% CI 0.23, 2.24) than adjunctive treatment of pramipexole-ER. Pramipexole-ER may be less likely to induce somnolence as an AE compared with ropinirole-SR (HR 0.46; 95% CI 0.23, 0.89). However, there were no statistically significant differences in UPDRS-motor score reduction, incidence of dyskinesia, hallucination, hypotension, insomnia and nausea, or withdrawals due to AE, for any reason.ConclusionAdjunctive therapy with ropinirole-SR or pramipexole appears to offer similar efficacy and tolerability in patients with advanced PD on the basis of this indirect comparison.FundingGSK