Influence of motor fluctuations duration, levodopa dose and duration of use in efficacy responses of Parkinson's disease patients: Post-hoc analysis from combined BIPARK-I and II

A Santos,A Lees,J Ferreira,O Rascol,A Antonini,F Ikedo,D Magalhaes,F Rocha,P Soares-Da-Silva,N Savic

doi:10.1016/j.jns.2019.10.1173

Abstract

To evaluate the impact of motor fluctuations (MF) duration, levodopa dose and levodopa duration of use (LDU) in efficacy responses of levodopa-treated Parkinson's Disease (PD) patients with MF. Opicapone (OPC), a once-daily COMT inhibitor, proved effective in the treatment of MF in PD 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. 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]. This post-hoc analysis assessed influence of MF duration (years), levodopa dose (mg) and LDU (years) in efficacy outcomes (OFF-/ON-time change from baseline). Applied linear regression's slope was statistically tested for deviation from zero. 1027 patients were randomized to BIPARK-I and II; Full Analysis Set comprised 517 [PLC (n = 255); OPC-50 mg (n = 262)]. Due to lack of matched-patients, four OPC-50 mg patients (MF > 12 years) were excluded from MF analysis and two PLC (<1 year) and five OPC-50 mg (>18 years) patients were excluded from LDU analysis. Mean baseline values were 2.4 (PLC) to 2.5 (OPC-50 mg) years of MF, 696 mg (PLC) to 698 mg (OPC-50 mg) of levodopa and 6.4 (PLC) to 6.0 (OPC-50 mg) years of use. OFF-/ON-time magnitude of responses was not influenced by any parameter. Linear regression was non-significant for each arm and variables analyzed. MF duration, levodopa dose and LDU do not appear to impact OFF-/ON-time magnitude of responses in a clinical study setting.

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