| アブストラクト | BACKGROUND: Istradefylline, a selective adenosine A(2A) receptor antagonist, is approved as an adjunct to levodopa in Parkinson's disease, but its long-term effects on clinically meaningful outcomes are unclear. OBJECTIVE: We aimed to compare the association of istradefylline versus catechol-O-methyltransferase (COMT) inhibitors with mortality, treatment escalation, and disease progression in levodopa-treated Parkinson's disease. METHODS: We conducted a nationwide cohort study emulating a target trial using the DeSC claims database in Japan. Patients aged >/=50 years with levodopa-treated Parkinson's disease between 2014 and 2023 were included. Strategies were initiation of istradefylline versus COMT inhibitors. Primary outcomes were all-cause mortality, levodopa-equivalent daily dose (LEDD) escalation to >/=1100 mg, and dementia or psychosis. Secondary outcomes were fractures, cardiovascular events, pneumonia, and depression. Intention-to-treat and per-protocol effects were estimated using Cox models with propensity score-based overlap weighting. RESULTS: We identified 3190 istradefylline and 7986 COMT inhibitor initiators. In intention-to-treat analysis, istradefylline was associated with lower risks of mortality (hazard ratio [HR] 0.91; 95 % CI 0.84-0.99) and LEDD escalation (HR 0.83; 95 % CI 0.73-0.94). Associations were stronger in per-protocol analysis (mortality: HR 0.84, 95 % CI 0.72-0.97; LEDD escalation: HR 0.71, 95 % CI 0.59-0.84). Istradefylline was linked to higher fracture risk (intention-to-treat HR 1.13, 95 % CI 1.02-1.25; per protocol HR 1.23, 95 % CI 1.07-1.41). No differences were observed for dementia, psychosis, or other outcomes. CONCLUSIONS: Istradefylline was associated with reduced mortality and treatment escalation but increased fracture risk compared with COMT inhibitors, supporting further evaluation of adenosine A(2A) antagonists. |
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| ジャーナル名 | Parkinsonism & related disorders |
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| Pubmed追加日 | 2026/2/5 |
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| 投稿者 | Ju, Chengsheng; Kubota, Kiyoshi; Xiong, Xi; Sato, Tsugumichi; Carroll, Camille; Schrag, Anette; Wei, Li; Foltynie, Thomas |
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| 組織名 | Research Department of Practice and Policy, UCL School of Pharmacy, London,;United Kingdom.;NPO Drug Safety Research Unit Japan, Tokyo, Japan.;Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan.;Translational and Clinical Research Institute, Newcastle University,;Newcastle-upon-Tyne, United Kingdom; Translational and Clinical Research;Institute, Newcastle University National Institute for Health and Care Research;(NIHR) Newcastle Biomedical Research Centre (BRC), Newcastle University, United;Kingdom.;Department of Clinical and Movement Neurosciences, UCL Institute of Neurology,;London, United Kingdom.;United Kingdom; Centre for Medicines Optimisation Research and Education,;University College London Hospitals National Health Service (NHS) Foundation;Trust, London, United Kingdom. Electronic address: l.wei@ucl.ac.uk.;London, United Kingdom. Electronic address: t.foltynie@ucl.ac.uk. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/41637901/ |
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