Effects of rasagiline on Parkinson's Disease Questionnaire (PDQ-39) emotional well-being domain in patients with Parkinson's disease: A post-hoc analysis of clinical trials in Japan.

Nobutaka Hattori,Atsushi Takeda,Masahiro Nagai,Ryosuke Takahashi,Masaki Arai,Hideki Mochizuki,Yoshihiko Furusawa,Tadayuki Kitagawa,Yuki Hanya,Andrea Martinuzzi

doi:10.1371/journal.pone.0262796

Abstract

BackgroundIdentifying the factors that influence health-related quality of life (HRQoL) is of great scientific interest, but a potential causal relationship between treatment and HRQoL has yet to be fully elucidated. Japanese patients reported better HRQoL outcomes on the Parkinson’s Disease Questionnaire (PDQ-39) emotional well-being domain, a 6-question subset of the PDQ-39 which is considered to reflect the emotional aspects of the disease-specific HRQoL, when treated with rasagiline, than placebo, in both a monotherapy clinical trial (NCT02337725) and an adjunctive therapy clinical trial in patients with wearing-off phenomena (NCT02337738).ObjectiveTo investigate how rasagiline exerts its effect on the PDQ-39 emotional well-being domain in Japanese patients with Parkinson’s disease.MethodsA path analysis was performed to assess the direct treatment effects of rasagiline on the PDQ-39 emotional well-being domain and the effects mediated indirectly through the influence on items related to motor symptoms by a post-hoc analysis of two clinical trials in Japan.ResultsIn the monotherapy trial, the PDQ-39 emotional well-being domain was mainly affected indirectly through items related to motor symptoms (80.7%) composed of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II (67.2%) and Part III (13.5%). In the adjunctive therapy trial, the PDQ-39 emotional well-being domain was also mainly influenced indirectly through effects on items related to motor symptoms (1 mg/day: 54.7%, 0.5 mg/day: 57.6%) composed of MDS-UPDRS Part II (1 mg/day: 35.6%, 0.5 mg/day: 40.9%), Part III (1 mg/day: 8.0%, 0.5 mg/day: 8.3%) and mean daily OFF-time (1 mg/day: 11.1%, 0.5 mg/day: 8.4%).ConclusionsThe effects of rasagiline on the PDQ-39 emotional well-being domain were mediated primarily by influence on the subjective aspects of motor experiences of daily living.

Highlights

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is classically characterized by symptoms such as bradykinesia, muscular rigidity, rest tremor, and postural and gait impairment [1]
The PDQ-39 emotional well-being domain was mainly affected indirectly through items related to motor symptoms (80.7%) composed of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II (67.2%) and Part III (13.5%)
In the adjunctive therapy trial, the PDQ-39 emotional well-being domain was mainly influenced indirectly through effects on items related to motor symptoms (1 mg/day: 54.7%, 0.5 mg/day: 57.6%) composed of MDS-UPDRS Part II (1 mg/day: 35.6%, 0.5 mg/day: 40.9%), Part III (1 mg/day: 8.0%, 0.5 mg/day: 8.3%) and mean daily OFF-time (1 mg/day: 11.1%, 0.5 mg/day: 8.4%)

Summary

Introduction

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is classically characterized by symptoms such as bradykinesia, muscular rigidity, rest tremor, and postural and gait impairment [1]. Rasagiline, a selective and irreversible inhibitor of monoamine oxidase B [7, 8], has been shown to be efficacious at relieving the symptoms of PD and is well-tolerated when administered as monotherapy, or as an adjunct to levodopa, in Japanese patients with PD in two randomized, double-blind, placebo-controlled, 26-week studies [9, 10]. In these studies, significant improvements in total and subscale scores were recorded using a validated Japanese translation of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) [9,10,11]. Japanese patients reported better HRQoL outcomes on the Parkinson’s Disease Questionnaire (PDQ-39) emotional well-being domain, a 6-question subset of the PDQ-39 which is considered to reflect the emotional aspects of the disease-specific HRQoL, when treated with rasagiline, than placebo, in both a monotherapy clinical trial (NCT02337725) and an adjunctive therapy clinical trial in patients with wearing-off phenomena (NCT02337738)

Methods

Results

Conclusion