{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:10:12Z","timestamp":1782738612999,"version":"3.54.5"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Limited trials are evaluating the efficacy of monoamine oxidase B inhibitors as an adjunct to levodopa monotherapy for early wearing-off in Parkinson\u2019s disease (PD). We evaluated the efficacy and safety of safinamide in patients with fluctuating PD treated with levodopa monotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This pooled analysis used data from the J-SILVER and KEEP studies and targeted patients with PD experiencing wearing-off who received safinamide as adjunct to levodopa monotherapy. Efficacy endpoints were mean changes in 39-item Parkinson\u2019s Disease Questionnaire (PDQ-39), Movement Disorder Society-Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS) Parts III and IV, and daily OFF time at 18\u202fweeks of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 54 patients (J-SILVER, <jats:italic>N<\/jats:italic>\u202f=\u202f24; KEEP, <jats:italic>N<\/jats:italic>\u202f=\u202f30), 41 completed the studies. Although not statistically significant, the change in PDQ-39 Summary Index exceeded the minimal clinical important difference (mean [standard deviation (SD)]: \u22122.2 [7.5], <jats:italic>p<\/jats:italic>\u202f=\u202f0.094) at Week 18. Significant improvements in MDS-UPDRS Parts III and IV scores and daily OFF time were observed at Week 18 from baseline (mean [SD]: \u22122.8 [8.5]; <jats:italic>p<\/jats:italic>\u202f=\u202f0.043, \u22121.3 [2.7]; <jats:italic>p<\/jats:italic>\u202f=\u202f0.004, and \u22121.2 [3.5] hours; <jats:italic>p<\/jats:italic>\u202f=\u202f0.041, respectively). Adverse events occurred in 24 patients (43.6%) and adverse drug reactions (ADRs) occurred in 12 patients (21.8%). ADRs with an incidence \u22655% were dyskinesia (3 events, 5.5%). In subgroup analyses, improvements in PDQ-39 Summary Index and MDS-UPDRS Parts III and IV were significant in patients aged \u226575\u202fyears (<jats:italic>p<\/jats:italic>\u202f=\u202f0.039, <jats:italic>p<\/jats:italic>\u202f=\u202f0.029, and <jats:italic>p<\/jats:italic>\u202f=\u202f0.025, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Safinamide as an adjunct to levodopa monotherapy was effective for early wearing-off without any new tolerability concerns. Safinamide was particularly beneficial in elderly patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1591664","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T04:10:45Z","timestamp":1748837445000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Safinamide as an adjunct to levodopa monotherapy in Asian patients with Parkinson\u2019s disease experiencing early wearing-off: a pooled analysis of the J-SILVER and KEEP studies"],"prefix":"10.3389","volume":"16","author":[{"given":"Noriko","family":"Nishikawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do-Young","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kogo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Hatano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Whan","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chizuru","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Shiiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JiEun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Sam","family":"Baik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.37349\/ent.2023.00036","article-title":"Pathophysiology of non-motor signs in Parkinson\u2019s disease: some recent updating with brief presentation","volume":"3","author":"Radad","year":"2023","journal-title":"Explor Neuroprot Ther"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"S31","DOI":"10.1016\/S1353-8020(09)70009-4","article-title":"Levodopa therapeutics for Parkinson\u2019s disease: new developments","volume":"15","author":"LeWitt","year":"2009","journal-title":"Parkinsonism Relat Disord"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1162016","DOI":"10.3389\/fneur.2023.1162016","article-title":"Prescribing patterns and determinants for elderly patients with Parkinson\u2019s disease in Japan: a retrospective observational study using insurance claims databases","volume":"14","author":"Seki","year":"2023","journal-title":"Front Neurol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1080\/14737175.2023.2176220","article-title":"Optimizing levodopa therapy, when and how? 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