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Observational Study
. 2023 May 15:448:120619.
doi: 10.1016/j.jns.2023.120619. Epub 2023 Mar 22.

Risk factors for developing dyskinesia among Parkinson's disease patients with wearing-off: J-FIRST

Takayasu Mishima  1 , Shih-Wei Chiu  2 , Hidemoto Saiki  3 , Takuhiro Yamaguchi  2 , Yasushi Shimo  4 , Tetsuya Maeda  5 , Hirohisa Watanabe  6 , Kenichi Kashihara  7 , Masahiro Nomoto  8 , Nobutaka Hattori  4 , Yoshio Tsuboi  9 ; J-FIRST Group
Affiliations
Free article
Observational Study

Risk factors for developing dyskinesia among Parkinson's disease patients with wearing-off: J-FIRST

Takayasu Mishima et al. J Neurol Sci. .
Free article

Abstract

Background: Dyskinesia frequently occurs during long-term treatment with levodopa in patients with Parkinson's disease (PD) and impacts quality of life. Few studies have examined risk factors for developing dyskinesia in PD patients exhibiting wearing-off. Therefore, we investigated the risk factors and impact of dyskinesia in PD patients exhibiting wearing-off.

Methods: We investigated the risk factors and impact of dyskinesia in a 1-year observational study of Japanese PD patients exhibiting wearing-off (J-FIRST). Risk factors were assessed by logistic regression analyses in patients without dyskinesia at study entry. Mixed-effect models were used to evaluate the impact of dyskinesia on changes in Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) Part I and PD Questionnaire (PDQ)-8 scores from one timepoint before dyskinesia was observed.

Results: Of 996 patients analyzed, 450 had dyskinesia at baseline, 133 developed dyskinesia within 1 year, and 413 did not develop dyskinesia. Female sex (odds ratio [95% confidence interval]: 2.636 [1.645-4.223]) and administration of a dopamine agonist (1.840 [1.083-3.126]), a catechol-O-methyltransferase inhibitor (2.044 [1.285-3.250]), or zonisamide (1.869 [1.184-2.950]) were independent risk factors for dyskinesia onset. MDS-UPDRS Part I and PDQ-8 scores increased significantly after the onset of dyskinesia (least-squares mean change [standard error] at 52 weeks: 1.11 [0.52], P = 0.0336; 1.53 [0.48], P = 0.0014; respectively).

Conclusion: Female sex and administration of a dopamine agonist, a catechol-O-methyltransferase inhibitor, or zonisamide were risk factors for dyskinesia onset within 1 year in PD patients exhibiting wearing-off. Nonmotor symptoms and quality of life deteriorated after dyskinesia onset.

Keywords: Dyskinesia; Nonmotor symptoms; Parkinson's disease; Quality of life; Wearing-off.

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Conflict of interest statement

Declaration of Competing Interest T. Mishima reports research funds from Kyowa Kirin in relation to this work. S.-W.C. reports research funds from Kyowa Kirin in relation to this work. H.S. reports research funds from Kyowa Kirin in relation to this work; research grants from Otsuka Pharmaceutical and Eisai; and honoraria from Kyowa Kirin, Eisai, Takeda Pharmaceutical, Dainippon Sumitomo Pharma, Ono Pharmaceutical, Otsuka Pharmaceutical, Novartis, Boston Scientific Japan, AbbVie, Medtronic Japan, and Teijin Pharma. T.Y. reports payments made to the institution from Kyowa Kirin in relation to this work; research grants from AC Medical, A2 Healthcare Corporation, EP Croit, ClinChoice, Japan Tobacco, Japan Media Corporation, Medidata Solutions, Ono Pharmaceutical, Asahi Intecc, 3H Clinical Trial, Medrio, Nipro Corporation, Intellim Corporation, Welby, 3H Medi Solution, Baseconnect, Nobori, Puravida Technologies, and Hemp Kitchen; research grants/payments to the institution from Kyowa Kirin, Tsumura & Co, Daiichi Sankyo, Otsuka Pharmaceutical, and Eisai; consulting fees from EP Croit, Japan Tobacco, Medidata Solutions, Ono Pharmaceutical, Kowa Company, Chugai Pharmaceutical, Tsumura & Co., Daiichi Sankyo, Eisai, Asahi Intecc, Asahi Kasei Pharma Corporation, 3H Clinical Trial, Intellim Corporation, Takeda, AstraZeneca, Sonire Therapeutics, and Seikagaku Corporation; payments or honoraria from Nipro Corporation; and participation on a data safety monitoring board or advisory board for Incyte Biosciences Japan. Y.S. reports research funds from Kyowa Kirin in relation to this work. T. Maeda reports research funds from Kyowa Kirin in relation to this work; lecture fees and scholarship donations from Daiichi Sankyo; lecture fees from Nihon Mediphysics, Biogen, Chugai Pharmaceutical, Kyowa Kirin, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Ono Pharmaceutical, Eisai, and Japan Medtronic; scholarship donations from Bayer Yakuhin, Teijin, and CSL Behring; and consulting fees from Kyowa Kirin and Ono Pharmaceutical. H.W. reports research funds from Kyowa Kirin in relation to this work; and honoraria from Takeda Pharmaceutical, AbbVie, Kyowa Kirin, Sumitomo Dainippon Pharma, Novartis, Otsuka Pharmaceutical, and FP Corporation. K.K. reports research funds from Kyowa Kirin in relation to this work; lecture fees and consulting fees from Kyowa Kirin; and lecture fees from Takeda Pharmaceutical and Ono Pharmaceutical. M.N. reports research funds from Kyowa Kirin in relation to this work; research funds from Kyowa Kirin, Kissei Pharmaceutical, and Hisamitsu Pharmaceutical; and lecture fees from Ehime University School of Medicine, Eisai, and Kyowa Kirin. N.H. reports grants to the Collaborative Research Department of Drug Discovery Research for Synucleopathies, lecture fees, and support for attending advisory boards from Kyowa Kirin in relation to this work; research contracts with Dainippon Sumitomo Pharma, Biogen Japan, and CellSource; consultancy fees from Hisamitsu Pharma and PARKINSON Laboratories; honoraria from Dainippon Sumitomo Pharma, Takeda Pharmaceutical, AbbVie, Nippon Boehringer Ingelheim, Otsuka Pharmaceutical, Novartis, Bristol-Myers Squibb, Ono Pharmaceutical, FP Pharmaceutical, Eisai, Kissei Pharmaceutical, Nihon Mediphysics, and Daiichi Sankyo; support for attending advisory boards from Dainippon Sumitomo Pharma, Takeda Pharmaceutical, Teijin Pharma, Novartis, Ono Pharmaceutical, Biogen Idec Japan, Kissei Pharmaceutical, and Mitsubishi Tanabe Pharma; Japanese (2021–0001888; Differential Diagnosis of Parkinson's Disease and Multiple System Atrophy, Patent Applicants: Juntendo University, Nagasaki University, January 4, 2021) and international (International filing date: 2021/09/22; priority date: 2020/10/29; applicant name: Juntendo Educational Foundation) patents; honoraria for team leader role at RIKEN: Center for Brain Science; and holds stock in PARKINSON Laboratories. Y.T. reports research funds from Kyowa Kirin; lecture fees from Sumitomo Dainippon Pharma, Takeda Pharmaceutical Company, Novartis, AbbVie, Otsuka Pharmaceutical, Ono Pharmaceutical, and Eisai; and contributes to courses run by Sunwels and Nipro Corporation.

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