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

Abstract

Background: Identifying 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).

Objective: To investigate how rasagiline exerts its effect on the PDQ-39 emotional well-being domain in Japanese patients with Parkinson's disease.

Methods: A 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.

Results: In 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%).

Conclusions: The 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.

Conflict of interest statement

The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: YH, TK, MA, and YF are paid employees of Takeda Pharmaceutical Company Limited. NH received lecture fees and grants from Takeda Pharmaceutical Co., Ltd. AT has served on advisory boards for Takeda Pharmaceutical Co., Ltd.; and has received honoraria from Takeda Pharmaceutical Co., Ltd. HM has served on advisory boards for Takeda Pharmaceutical Co., Ltd. MN has served on advisory boards for Takeda Pharmaceutical Co., Ltd.; and has received honoraria from Takeda Pharmaceutical Co., Ltd. RT has performed corporate-sponsored research for Takeda Pharmaceutical Co., Ltd. There are no patents to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Hypothesized path diagrams in the…
Fig 1. Hypothesized path diagrams in the monotherapy trial in early PD.
P1 through P6 stand for the path coefficients (standardized regression coefficient) of each path. Covariances between exogeneous variables are not shown to aid in readability. aChange from baseline. LOCF, last observation carried forward; MDS-UPDRS, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale; PDQ-39 EWB, Emotional well-being domain of the 39-item Parkinson’s disease questionnaire.
Fig 2. Hypothesized path diagrams in the…
Fig 2. Hypothesized path diagrams in the adjunctive therapy trial in PD patients with wearing-off phenomena.
P7 through P18 stand for the path coefficients (standardized regression coefficient) of each path. Covariances between exogeneous variables are not shown to aid in readability. aChange from baseline. LOCF, last observation carried forward; MDS-UPDRS, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale; PDQ-39 EWB, Emotional well-being domain of the 39-item Parkinson’s disease questionnaire.

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