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During the double-blind period, prasinezumab-treated individuals showed less progression of motor signs (Movement Disorders Society-sponsored revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS\u2013UPDRS) Part\u2009III) than placebo-treated individuals. We evaluated whether the effect of prasinezumab on motor progression, assessed as a change in MDS\u2013UPDRS Part\u2009III score in the OFF and ON states, and MDS\u2013UPDRS Part\u2009II score, was sustained for 4\u2009years from the start of the trial. We compared participants enrolled in the PASADENA open-label extension study with those enrolled in an external comparator arm derived from the Parkinson\u2019s Progression Markers Initiative observational study. The PASADENA delayed-start (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200994) and early-start (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009177) groups showed a slower decline (a smaller increase in score) in MDS\u2013UPDRS Part\u2009III scores in the OFF state (delayed start, \u221251%; early start, \u221265%), ON state (delayed start, \u221294%; early start, \u2212118%) and MDS\u2013UPDRS Part\u2009II (delayed start, \u221248%; early start, \u221240%) than did the Parkinson\u2019s Progression Markers Initiative external comparator (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009303). This exploratory analysis, which requires confirmation in future studies, suggested that the effect of prasinezumab in slowing motor progression in PD may be sustained long term. PASADENA ClinicalTrials.gov no.\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03100149\">NCT03100149<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-024-03270-6","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T06:18:43Z","timestamp":1728368323000},"page":"3669-3675","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Sustained effect of prasinezumab on Parkinson\u2019s disease motor progression in the open-label extension of the PASADENA trial"],"prefix":"10.1038","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6247-8988","authenticated-orcid":false,"given":"Gennaro","family":"Pagano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabelle","family":"Monnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Reyes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Ribba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1910-586X","authenticated-orcid":false,"given":"Hanno","family":"Svoboda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kustermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Simuni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald B.","family":"Postuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Pavese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Stocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7515-8596","authenticated-orcid":false,"given":"Kathrin","family":"Brockmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Smigorski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Gerbaldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo","family":"Fontoura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachelle","family":"Doody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey A.","family":"Kerchner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Brundin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Marek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azad","family":"Bonni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Nikolcheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"PASADENA Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Prasinezumab Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"3270_CR1","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1517\/14728222.2012.674111","volume":"16","author":"K Vekrellis","year":"2012","unstructured":"Vekrellis, K. & Stefanis, L. 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Hoffmann-La Roche Ltd. R.D. is also employed by Genentech. P.B. also has ownership interests in Acousort AB, Enterin Inc, Axial Therapeutics and Kenai Therapeutics. H.S. is an employee of Roche Diagnostics GmbH Deutschland and a shareholder of F. Hoffmann-La Roche. In the past 12\u2009months, T.S. has served as a consultant for AskBio, Amneal, BlueRock Therapeutics, Critical Path for Parkinson\u2019s Consortium, Denali, General Electric, Kyowa, Neuroderm\/MTPA, Prevail\/Lilly, Roche, Sanofi, Sinopia, Takeda and Vanqua Bio. T.S. has served on advisory boards for AskBio, Amneal, Biohaven, Denali, GAIN, General Electric, Kyowa, The Michael J. Fox Foundation, Neuron23, Parkinson Study Group, Prevail\/Lilly and Roche. T.S. has also served as a member of the scientific advisory board of Koneksa, Neuroderm\/MTPA, Sanofi and UCB, has received research funding from Amneal, Biogen, Neuroderm, Prevail, Roche and UCB and is an investigator for the National Institute of Neurological Disorders and Stroke, The Michael J. Fox Foundation and the Parkinson\u2019s Foundation. R.B.P. reports grants and personal fees from Fonds de la Recherche en Sante, grants from the Canadian Institute of Health Research, grants from The Michael J. Fox Foundation, grants from Webster Foundation, personal fees from Biogen, personal fees from Curasen, personal fees from Novartis, personal fees from Eisai, other from Parkinson Canada, grants from National Institutes of Health, personal fees from International Parkinson and Movement Disorders Society, personal fees from Merck, personal fees from Vaxxinity, personal fees from Bristol Myers Squibb, personal fees from Clinilabs, personal fees from Ventus, personal fees from Korro and personal fees from Calico. R.B.P. also received consulting fees from Roche for helping to plan and interpret the study. N.P. reports participation in advisory boards for Britannia, Boston Scientific, Benevolent AI, Hoffmann-La Roche, Inc. and Abbvie. N.P. also reports receiving honoraria from Britannia, Abbvie, GE Healthcare and Boston Scientific, and grants from the Independent Research Fund Denmark, Danish Parkinson\u2019s disease Association, Parkinson\u2019s UK, Center of Excellence in Neurodegeneration network award, GE Healthcare Grant, Multiple System Atrophy Trust, Weston Brain Institute, EU Joint Program Neurodegenerative Disease Research, EU Horizon 2020 research, The Michael J. Fox Foundation for Parkinson\u2019s Research and F. Hoffmann-La Roche, Inc. F.S. is a consultant for AbbVie, Bial Pharma, Biogen, F. Hoffmann-La Roche Ltd., H. Lundbeck A S, Mitsubishi Tanabe Pharma America, Inc., Sunovion Pharmaceuticals, Inc., Teva Pharmaceutical Industries, Zambon and Britannia. K.B. has received research funding from The Michael J. Fox Foundation for Parkinson\u2019s Research, the German Society for Parkinson DPG, the Health Forum Baden Wuerttemberg, the Else Kr\u00f6ner Fresenius Stiftung, the University of Tuebingen and the German Research Foundation DFG. K.B. is a consultant for F. Hoffmann-La Roche Ltd., Vanqua Bio and The Michael J. Fox Foundation for Parkinson\u2019s Research, and has received speaker honoraria from Abbvie, Lundbeck, UCB and Zambon. V.G. is a full-time employee of Excelya Germany GmbH and was an external business partner of F. Hoffmann-La Roche Ltd. K.M. is a consultant for The Michael J. Fox Foundation for Parkinson\u2019s Research, F. Hoffmann-La Roche Ltd UCB, Denali, Takeda, Biohaven, Neuron23, Aprinoia, Prothena, Calico, Inhibikase, Invicro, Koneksa and Lilly.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}