Incidence of treatment-emergent adverse events in Parkinson's disease patients according to baseline mao-b inhibitors use: Post-hoc analysis from double-blind combined BIPARK-I and II data

Abstract

To evaluate the incidence of treatment-emergent adverse events (TEAEs) in levodopa-treated Parkinson's Disease (PD) patients with motor fluctuations and taking opicapone (OPC), a once-daily COMT inhibitor that proved effective in the treatment of motor fluctuations in PD patients in two large, pivotal, multinational trials (BIPARK-I and II) [[1]Ferreira et al.Lancet Neurol. 2016; 15: 154-165Google Scholar,[2]Lees et al.JAMA Neurol. 2017; 74: 197-206Google Scholar]. Patient-level data from matching treatment arms in BIPARK-I and II were combined in placebo (PLC) and OPC-50 mg groups. The studies had similar designs (primary efficacy endpoint: change from baseline in patient diaries-based absolute OFF-time) and eligibility criteria [[1]Ferreira et al.Lancet Neurol. 2016; 15: 154-165Google Scholar,[2]Lees et al.JAMA Neurol. 2017; 74: 197-206Google Scholar]. Safety was assessed by incidence of TEAEs, laboratory parameters, ECGs and vital signs. An exploratory post-hoc analysis was performed to evaluate the incidence of TEAEs according to baseline MAO-B inhibitors (MAOBi) use. Of the 1027 patients randomized to BIPARK-I and II, 522 patients took a dose of relevant study medication (OPC-50 mg n = 265, PLC n = 257) and were included in this analysis. Non-MAOBi user patients represented ~80% of both OPC-50 mg and PLC groups. In total, 64.2% of OPC-50 mg patients reported any TEAE compared to 57.2% in PLC. There was a comparable-to-overall incidence of TEAEs for non-MAOBi matched user patients (62.5% vs. 53.8% for OPC-50 mg and PLC groups). In contrast, for MAOBi-matched patients, incidence of TEAEs was lower in OPC-treated patients (70.2%) than PLC-treated ones (71.4%), but overall higher. Most frequently occurring TEAE was dyskinesia in both subgroups. Opicapone appears to be well-tolerated in both MAOBi and non-MAOBi user patients.