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Observational Study
. 2024 Oct 23;19(10):e0309297.
doi: 10.1371/journal.pone.0309297. eCollection 2024.

Prescription trends in Japanese advanced Parkinson's disease patients with non-motor symptoms: J-FIRST

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

Prescription trends in Japanese advanced Parkinson's disease patients with non-motor symptoms: J-FIRST

Masahiro Nomoto et al. PLoS One. .

Abstract

Background: Non-motor symptoms (NMS) are important factors when selecting treatments for patients with advanced Parkinson's disease (PD). We sought to elucidate the prescribing practices for advanced PD patients with NMS in Japanese clinical practice.

Methods: We examined the prescription rates and doses of anti-PD drugs, and the use of non-steroidal anti-inflammatory drugs (NSAIDs) in post hoc analyses of a 52-week observational study of 996 PD patients with wearing-off on levodopa-containing therapy and ≥1 NMS.

Results: Dopamine agonists were the most frequently prescribed drugs combined with levodopa-containing drugs, followed by entacapone, zonisamide, istradefylline, selegiline, and amantadine. The daily dose of levodopa-containing drugs, rotigotine, entacapone, istradefylline, and droxidopa, and the levodopa-equivalent dose increased during the observation period. In a subgroup analysis of patients stratified by NMS status (improved/unchanged/deteriorated), the deteriorated group had higher prescription rates of entacapone and istradefylline, whereas the improved group had higher prescription rates of NSAIDs and zonisamide at Week 52. Prescriptions varied by geographical region for anti-PD drugs and by NMS status for NSAIDs.

Conclusions: There were significant changes in the prescriptions and dosing of selected anti-PD drugs, especially newer drugs. Anti-PD drug and NSAID prescriptions also varied by changes in NMS status and geographic region.

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Conflict of interest statement

Masahiro Nomoto reported research funds from Kyowa Kirin in relation to this study; and reported employment by The Social Welfare Organization Imperial Gift Foundation Inc. Saiseikai Imabari Hospital; honoraria from Ehime University, Takeda Pharmaceutical, Kyowa Kirin, Eisai, and Ono Pharmaceutical; consultancies for Kissei Pharmaceutical and SNLD; and has served on advisory boards for the Pharmaceuticals and Medical Devices Agency and Ehime Prefecture. Yoshio Tsuboi reported research funds from Kyowa Kirin in relation to this study; and reported lecture fees from Sumitomo Pharma, Takeda Pharmaceutical, Novartis Pharma, Ono Pharmaceutical, and Eisai; and contributes to courses organized by SUNWELS and Nipro Corporation. Kenichi Kashihara reported research funds from Kyowa Kirin in relation to this study; and reported employment by Okayama Neurology Clinic; and honoraria from Kyowa Kirin, Takeda Pharmaceutical, Ono Pharmaceutical, Sumitomo Pharma, FP Corporation, AbbVie GK, and Eisai. Shih-Wei Chiu reported research funds from Kyowa Kirin in relation to this study. Tetsuya Maeda reported research funds from Kyowa Kirin in relation to this study; and reported lecture fees and scholarship donations from Sumitomo Pharma, Takeda Pharmaceutical Company, Ono Pharmaceutical, Eisai, Otsuka Pharmaceutical, Nippon Boehringer Ingelheim, Daiichi Sankyo, and Japan Medtronic; lecture fees from AbbVie, FP Corporation, Biogen, and Chugai Pharmaceutical; scholarship donations from Bayer Yakuhin, Teijin, and CSL Behring; and consulting fees from Kyowa Kirin and Ono Pharmaceutical. Hidemoto Saiki reported editorial support from Kyowa Kirin in relation to this study; and reported honoraria from Eisai, Sumitomo Pharma, Ono Pharmaceutical, Takeda Pharmaceutical, and Medtronic Japan; and grants from Otsuka Pharmaceutical and PDRadiopharma Inc. Hirohisa Watanabe reported research funds from Kyowa Kirin in relation to this study; and reported honoraria from Takeda Pharmaceutical, AbbVie, Kyowa Kirin, Sumitomo Pharma, Novartis Pharma, Otsuka Pharmaceutical, and FP Corporation. Yasushi Shimo reported honoraria from Takeda Pharmaceutical, Abbott Japan, Otsuka Pharmaceutical, Medtronic Japan, Kyowa Kirin, Eisai, MDS, Boston Scientific Japan, Sumitomo Pharma, Daiichi Sankyo, Nihon Medi-Physics, and EA Pharma; and a grant from Japan Society for the Promotion of Science (JSPS KAKENHI no. 21K07282). Nobutaka Hattori reported research grants, support for attending advisory boards, and support for a joint research department from Kyowa Kirin; and reported research contracts with Sumitomo Pharma and CellSource; consultancy fees from PARKINSON Laboratories; honoraria from Sumitomo Pharma, AbbVie, Otsuka Pharmaceutical, Novartis Pharma, Ono Pharmaceutical, FP Pharmaceutical, Eisai, and Daiichi Sankyo; support for attending advisory boards from Sumitomo Pharma, Novartis Pharma, Ono Pharmaceutical, Teijin Pharma, and Mitsubishi Tanabe Pharma Corporation; support for an endowed department from Nippon Boehringer Ingelheim, FP Pharmaceutical, Teijin Pharma, Fujifilm Wako Pure Chemical Corporation, and Meiji Seika Pharma; support for a joint research department from Kyowa Kirin, Sumitomo Pharma, Parkinson Laboratories, Takeda Pharmaceutical, Otsuka Pharmaceutical, Ono Pharmaceutical, Nihon Medi-Physics, Mitsubishi Tanabe Pharma Corporation, and Sunwels; scholarship donations from FP Pharmaceutical; holds stock in Parkinson Laboratories; honoraria for a team leader role at RIKEN Center for Brain Science; and is a coauthor on patent applications by Juntendo University. Takuhiro Yamaguchi reported grants from Otsuka Pharmaceutical, Solasia Pharma, Japan Tobacco Inc., Daiichi Sankyo, Eisai, and Cordis Corporation; and personal fees from Intellim Corporation, Chugai Pharmaceutical, SONIRE Therapeutics Inc., Merck and Co Inc., EPS Corporation, Japan Tobacco Inc., Ono Pharmaceutical, Kowa Company, Daiichi Sankyo, Eisai, 3H Clinical Trial Inc., and Incyte Biosciences Japan. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Prescription rates for antiparkinsonian drugs and non-steroidal anti-inflammatory drugs during the observation period for the overall sample.
Values were calculated as estimates (0.0–1.0) ± standard error and converted to percentages (0%–100%). *P < 0.05 for Week 52 vs. Week 0 (generalized linear model). NSAIDs: non-steroidal anti-inflammatory drugs.
Fig 2
Fig 2. Prescribed doses of antiparkinsonian drugs during the observation period for the overall sample.
(A) Levodopa-containing drugs. (B) Levodopa equivalent dose. (C) Pergolide. (D) Cabergoline. (E) Pramipexole. (F) Ropinirole. (G) Apomorphine. (H) Rotigotine. (I) Entacapone. (J) Selegiline. (K) Zonisamide. (L) Amantadine. (M) Istradefylline. (N) Droxidopa. Values are estimates ± standard error. The number of patients (%) prescribed each drug at Week 0 is indicated. *P < 0.05 for Week 52 vs. Week 0 (generalized linear model). LED: levodopa-equivalent dose.
Fig 3
Fig 3
Prescription rates of antiparkinsonian drugs and non-steroidal anti-inflammatory drugs during the observation period in patients divided according to the pattern of change in non-motor symptoms: improved (A), unchanged (B), and deteriorated (C). Values are estimates ± standard error. Symbols indicate significance at a level of α = 0.05 (generalized linear model): *zonisamide—improved group vs. unchanged group; †NSAIDs—improved group vs. unchanged and deteriorated groups; ‡entacapone—deteriorated group vs. improved and unchanged groups; §istradefylline—deteriorated group vs. unchanged group. NSAIDs: non-steroidal anti-inflammatory drugs.
Fig 4
Fig 4
Prescribed doses of levodopa-containing drugs (A) and the levodopa-equivalent dose (B) during the observation period for the improved, unchanged, and deteriorated groups. Values are estimates ± standard error. The number of patients (%) in each group is indicated. *P < 0.05 for Week 52 vs. Week 0 (generalized linear model). LED: levodopa-equivalent dose.
Fig 5
Fig 5
Prescription rates for antiparkinsonian drugs and non-steroidal anti-inflammatory drugs during the observation period for West (A) and East (B) Japan. Values were calculated as estimates (0.0–1.0) and converted to percentages (0%–100%). NSAIDs: non-steroidal anti-inflammatory drugs.
Fig 6
Fig 6
Prescribed doses of levodopa-containing drugs (A) and the levodopa-equivalent dose (B) during the observation period for West and East Japan. Values are estimates ± standard error. LED: levodopa-equivalent dose.
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