Rotigotine in Combination with the MAO-B Inhibitor Selegiline in Early Parkinson's Disease: A Post Hoc Analysis

Background: Monoamine oxidase B ( MAO-B) inhibitors and dopamine receptor agonists are common first-line treatment options in early Parkinson's disease ( PD). Objective: To evaluate the efficacy and safety of rotigotine transdermal patch as an add-on therapy to an MAO-B inhibitor in patients with early-PD. Methods: In two Phase III, randomized, double-blind, placebo-controlled studies in early-PD (SP512, SP513), patients were randomized to rotigotine (titrated to optimal dose <= 8 mg/24 h) or placebo, and maintained for 24 (SP512) or 33 (SP513) weeks. Post hoc analyses were performed on pooled data for patients receiving an MAO-B inhibitor (selegiline) at a stable dose at randomization and throughout the studies, with groups defined as Selegiline+Rotigotine and Selegiline+Placebo. Outcome measures included change from baseline in Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living), III (motor), UPDRS II+III and responders (patients achieving >= 20%, >= 25% or >= 30% decrease in UPDRS II+III). As post hoc analyses, p-values are exploratory. Results: 130 patients were evaluable for efficacy analyses (Selegiline+Rotigotine: 84, Selegiline+Placebo: 46). Combined treatment with rotigotine and selegiline improved UPDRS III and UPDRS II+III scores versus selegiline alone (LS-mean [95% CI] treatment difference for UPDRS III: -4.89 [-7.87 to -1.91], p = 0.0015; for UPDRS II+III: -5.76 [-9.71 to -1.82], p = 0.0045). Higher proportion of patients in the Selegiline+Rotigotine group were classified as >= 20%, >= 25% or >= 30% responders (all p < 0.001). Combined treatment appeared more effective in patients aged <= 65 years versus > 65 years (although patient numbers in the subgroups were low). Adverse event profile was consistent with the known safety profile of rotigotine. Conclusions: In these post hoc analyses, adjunctive treatment with rotigotine in patients already receiving an MAO-B inhibitor improved UPDRS II+III score; this appeared to be largely driven by improvements in the motor aspects of PD.