The Efficacy and Safety of Piribedil Relative to Pramipexole for the Treatment of Early Parkinson Disease: A Systematic Literature Review and Network Meta-Analysis

OBJECTIVES Patients with early Parkinson disease (PD) frequently defer initiation of levodopa treatment to minimize long-term complications. Nonergoline dopamine agonists, such as pramipexole and piribedil, are frequent first-line therapies for early PD patients, yet limited head-to-head randomized controlled trial (RCT) evidence exists for dopamine agonists in this population. We therefore conducted a systematic literature review and network meta-analysis. METHODS MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched (until January 7, 2020), identifying RCTs assessing the efficacy of piribedil or pramipexole in early PD. Eligible trial data were incorporated into fixed- and random-effects Bayesian network meta-analyses. RESULTS No RCTs were identified directly comparing piribedil with pramipexole, but 6 trials provided data for pramipexole versus placebo and 2 compared piribedil versus placebo, facilitating indirect comparisons. Across all time points assessed, no significant differences were found between pramipexole and piribedil for change in the Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline. Piribedil and pramipexole demonstrated superiority relative to placebo for UPDRS II/III change at weeks 22 to 30. No significant differences were noted between the treatments at weeks 20 to 35 for anxiety, constipation, hypotension, nausea, and somnolence. Sensitivity analyses on adjustment for dose titration periods and baseline risk yielded the same pattern of results. CONCLUSIONS No significant differences were found for pramipexole versus piribedil in the UPDRS II/III scores from baseline in early PD, with similar safety profiles.