Objective: To evaluate the direct and indirect effects of rasagiline on emotional well-being domain of the PDQ-39 in patients with PD by a post-hoc analysis of clinical trials in Japan.

Background: In the clinical trials of rasagiline in Japan, monotherapy in early PD (NCT02337725, Phase 3) and adjunctive therapy in PD patients with wearing-off phenomena (NCT02337738, Phase 2/3), the least squares mean differences vs. placebo for change from baseline on the PDQ-39 emotional well-being domain score, MDS-UPDRS Part II total score, Part III total score and mean daily OFF-time at week 26 (LOCF) favored rasagiline [1][2]. Identifying the factors that influence Health-Related Quality of Life (HRQoL) is of great scientific interest [3], but a possible causal relationship between treatment and HRQoL has yet to be fully elucidated [4].

Method: A path analysis was performed using SAS 9.4 Proc CALIS in order 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, specifically MDS-UPDRS Part II and Part III in the monotherapy trial and MDS-UPDRS Part II, Part III and mean daily OFF-time in the adjunctive therapy trial. All items were calculated as change from baseline at week 26 (LOCF).

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 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 (1.0 mg/day: 54.7%, 0.5 mg/day: 57.6%) composed of MDS-UPDRS Part II (1.0 mg/day: 35.6%, 0.5 mg/day: 40.9%), Part III (1.0 mg/day: 8.0%, 0.5 mg/day: 8.3%) and mean daily OFF-time (1.0 mg/day: 11.1%, 0.5 mg/day: 8.4%).

Conclusion: This study indicated that the effects of rasagiline on the PDQ-39 emotional well-being domain were mediated primarily by influence on the MDS-UPDRS Part II. MDS-UPDRS Part II is a subjective assessment for motor aspects of experiences of daily living; therefore, alleviation of subjective motor-related symptoms of patients may be an appropriate clinical focus for influencing the subjective emotional aspects of HRQoL.

References: [1] Hattori N, Takeda A, Takeda S, Nishimura A, Kitagawa T, Mochizuki H, Nagai M, Takahashi R. Rasagiline monotherapy in early Parkinson’s disease: A phase 3, randomized study in Japan. Parkinsonism Relat Disord. 2019;60:146-52. [2] Hattori N, Takeda A, Takeda S, Nishimura A, Kato M, Mochizuki H, Nagai M, Takahashi R. Efficacy and safety of adjunctive rasagiline in Japanese Parkinson’s disease patients with wearing-off phenomena: A phase 2/3, randomized, double-blind, placebo-controlled, multicenter study. Parkinsonism Relat Disord. 2018;53:21-7. [3] Skorvanek M, Martinez-Martin P, Kovacs N, Zezula I, Rodriguez-Violante M, Corvol JC, Taba P, Seppi K, Levin O, Schrag A, Aviles-Olmos I, Alvarez-Sanchez M, Arakaki T, Aschermann Z, Benchetrit E, Benoit C, Bergareche-Yarza A, Cervantes-Arriaga A, Chade A, Cormier F, Datieva V, Gallagher DA, Garretto N, Gdovinova Z, Gershanik O, Grofik M, Han V, Kadastik-Eerme L, Kurtis MM, Mangone G, Martinez-Castrillo JC, Mendoza-Rodriguez A, Minar M, Moore HP, Muldmaa M, Mueller C, Pinter B, Poewe W, Rallmann K, Reiter E, Rodriguez-Blazquez C, Singer C, Valkovic P, Goetz CG, Stebbins GT. Relationship between the MDS-UPDRS and Quality of Life: A large multicenter study of 3206 patients. Parkinsonism Relat Disord. 2018;52:83-9. [4] Cattaneo C, Barone P, Bonizzoni E, Sardina M. Effects of Safinamide on Pain in Fluctuating Parkinson’s Disease Patients: A Post-Hoc Analysis. J Parkinsons Dis. 2017;7(1):95-101.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effects-of-rasagiline-on-parkinsons-disease-questionnaire-pdq-39-emotional-well-being-domain-in-patients-with-parkinsons-disease-pd-a-post-hoc-analysis-of-clinical-trials-in-jap/