{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T01:08:45Z","timestamp":1784077725844,"version":"3.55.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T00:00:00Z","timestamp":1737158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T00:00:00Z","timestamp":1737158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"name":"Teva Branded Pharmaceutical Products R&D, Inc."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["CNS Drugs"],"published-print":{"date-parts":[[2025,2]]},"DOI":"10.1007\/s40263-024-01139-3","type":"journal-article","created":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T02:10:19Z","timestamp":1737166219000},"page":"185-195","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Safety and Efficacy of Deutetrabenazine at High versus Lower Daily Dosages in the ARC-HD Study to Treat Chorea in Huntington Disease"],"prefix":"10.1007","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1866-162X","authenticated-orcid":false,"given":"Samuel","family":"Frank","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia M.","family":"Testa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jody","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Kayson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blair R.","family":"Leavitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Oakes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"O\u2019Neill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn","family":"Whaley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Gross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayla","family":"Chaijale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Barash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Forrest","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Huntington Study Group\/ARC-HD Investigators and Coordinators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,18]]},"reference":[{"issue":"1","key":"1139_CR1","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1136\/jnnp.66.1.52","volume":"66","author":"T Foroud","year":"1999","unstructured":"Foroud T, Gray J, Ivashina J, Conneally P. Differences in duration of Huntington\u2019s disease based on age at onset. J Neurol Neurosurg Psychiatry. 1999;66(1):52\u20136. https:\/\/doi.org\/10.1136\/jnnp.66.1.52.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"9","key":"1139_CR2","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/S1474-4422(09)70183-8","volume":"8","author":"J Jankovic","year":"2009","unstructured":"Jankovic J. Treatment of hyperkinetic movement disorders. Lancet Neurol. 2009;8(9):844\u201356. https:\/\/doi.org\/10.1016\/S1474-4422(09)70183-8.","journal-title":"Lancet Neurol"},{"key":"1139_CR3","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jns.2018.09.022","volume":"396","author":"CM Testa","year":"2019","unstructured":"Testa CM, Jankovic J. Huntington disease: a quarter century of progress since the gene discovery. J Neurol Sci. 2019;396:52\u201368. https:\/\/doi.org\/10.1016\/j.jns.2018.09.022.","journal-title":"J Neurol Sci"},{"issue":"10","key":"1139_CR4","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.1007\/s11136-016-1386-3","volume":"25","author":"NE Carlozzi","year":"2016","unstructured":"Carlozzi NE, Schilling SG, Lai J-S, Paulsen JS, Hahn EA, Perlmutter JS, et al. HDQLIFE: development and assessment of health-related quality of life in Huntington disease (HD). Qual Life Res. 2016;25(10):2441\u201355. https:\/\/doi.org\/10.1007\/s11136-016-1386-3.","journal-title":"Qual Life Res"},{"issue":"4","key":"1139_CR5","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1586\/14737175.2015.1025383","volume":"15","author":"LC Schwab","year":"2015","unstructured":"Schwab LC, Garas SN, Drouin-Ouellet J, Mason SL, Stott S, Barker RA. Dopamine and Huntington\u2019s disease. Expert Rev Neurother. 2015;15(4):445\u201358. https:\/\/doi.org\/10.1586\/14737175.2015.1025383.","journal-title":"Expert Rev Neurother"},{"key":"1139_CR6","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/B978-0-444-52014-2.00002-1","volume":"100","author":"KE Anderson","year":"2011","unstructured":"Anderson KE. Huntington\u2019s disease. Handb Clin Neurol. 2011;100:15\u201324. https:\/\/doi.org\/10.1016\/B978-0-444-52014-2.00002-1.","journal-title":"Handb Clin Neurol"},{"key":"1139_CR7","doi-asserted-by":"publisher","DOI":"10.1371\/currents.RRN1260","volume":"3","author":"JM Burgunder","year":"2011","unstructured":"Burgunder JM, Guttman M, Perlman S, Goodman N, van Kammen DP, Goodman L. An international survey-based algorithm for the pharmacologic treatment of chorea in Huntington\u2019s disease. PLoS Curr. 2011;3: RRN1260. https:\/\/doi.org\/10.1371\/currents.RRN1260.","journal-title":"PLoS Curr"},{"issue":"11","key":"1139_CR8","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1002\/mds.25996","volume":"29","author":"J Jankovic","year":"2014","unstructured":"Jankovic J, Roos RA. Chorea associated with Huntington\u2019s disease: to treat or not to treat? Mov Disord. 2014;29(11):1414\u20138. https:\/\/doi.org\/10.1002\/mds.25996.","journal-title":"Mov Disord"},{"key":"1139_CR9","unstructured":"Austedo\u00ae (deutetrabenazine) tablets [prescribing information]. Parsippany: Teva Neuroscience, Inc; 2023."},{"issue":"6","key":"1139_CR10","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/S1474-4422(23)00127-8","volume":"22","author":"E Furr-Stimming","year":"2023","unstructured":"Huntington Study Group KINECT-HD Collaborators, Furr-Stimming E, Claassen DO, Kayson E, Goldstein J, Mehanna R, Zhang H, et al. Safety and efficacy of valbenazine for the treatment of chorea associated with Huntington\u2019s disease (KINECT-HD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2023;22(6):494\u2013504. https:\/\/doi.org\/10.1016\/S1474-4422(23)00127-8.","journal-title":"Lancet Neurol"},{"key":"1139_CR11","unstructured":"Xenazine\u00ae (tetrabenazine) tablets [prescribing information]. Deerfield: Neopharm Ltd.; 2023."},{"issue":"8","key":"1139_CR12","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1080\/14656566.2021.1876666","volume":"22","author":"JS Gibson","year":"2021","unstructured":"Gibson JS, Claassen DO. State-of-the-art pharmacological approaches to reduce chorea in Huntington\u2019s disease. Expert Opin Pharmacother. 2021;22(8):1015. https:\/\/doi.org\/10.1080\/14656566.2021.1876666.","journal-title":"Expert Opin Pharmacother"},{"issue":"1","key":"1139_CR13","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s00228-021-03202-0","volume":"78","author":"F Schneider","year":"2022","unstructured":"Schneider F, Stamler D, Bradbury MJ, Loupe PS, Gordon MF, Rabinovich-Guilatt L. The effect of potent CYP2D6 inhibition on the pharmacokinetics and safety of deutetrabenazine in healthy volunteers. Eur J Clin Pharmacol. 2022;78(1):11\u20138. https:\/\/doi.org\/10.1007\/s00228-021-03202-0.","journal-title":"Eur J Clin Pharmacol"},{"issue":"1","key":"1139_CR14","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1001\/jama.2016.8655","volume":"316","author":"S Frank","year":"2016","unstructured":"Huntington Study Group, Frank S, Testa CM, Stamler D, Kayson E, Davis C, Edmondson MC, et al. Effect of deutetrabenazine on chorea among patients with Huntington disease: a randomized clinical trial. JAMA. 2016;316(1):40\u201350. https:\/\/doi.org\/10.1001\/jama.2016.8655.","journal-title":"JAMA"},{"issue":"11","key":"1139_CR15","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1007\/s40263-022-00956-8","volume":"36","author":"S Frank","year":"2022","unstructured":"Huntington Study Group\/ARC-HD Investigators and Coordinators, Frank S, Testa C, Edmondson MC, Goldstein J, Kayson E, Leavitt BR, et al. The safety of deutetrabenazine for chorea in Huntington disease: an open-label extension study. CNS Drugs. 2022;36(11):1207\u201316. https:\/\/doi.org\/10.1007\/s40263-022-00956-8.","journal-title":"CNS Drugs"},{"issue":"8","key":"1139_CR16","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1001\/jamaneurol.2017.1352","volume":"74","author":"S Frank","year":"2017","unstructured":"Huntington Study Group\/Alternatives for Reducing Chorea in Huntington Disease Investigators, Frank S, Stamler D, Kayson E, Claassen DO, Colcher A, Davis C, et al. Safety of converting from tetrabenazine to deutetrabenazine for the treatment of chorea. JAMA Neurol. 2017;74(8):977\u201382. https:\/\/doi.org\/10.1001\/jamaneurol.2017.1352.","journal-title":"JAMA Neurol"},{"issue":"8","key":"1139_CR17","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1002\/sim.2335","volume":"25","author":"GF Liu","year":"2006","unstructured":"Liu GF, Wang J, Liu K, Snavely DB. Confidence intervals for an exposure adjusted incidence rate difference with applications to clinical trials. Stat Med. 2006;25(8):1275\u201386. https:\/\/doi.org\/10.1002\/sim.2335.","journal-title":"Stat Med"},{"issue":"2","key":"1139_CR18","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1002\/mds.870110204","volume":"11","author":"Huntington Study Group","year":"1996","unstructured":"Huntington Study Group. Unified Huntington\u2019s Disease Rating Scale: reliability and consistency. Mov Disord. 1996;11(2):136\u201342. https:\/\/doi.org\/10.1002\/mds.870110204.","journal-title":"Mov Disord"},{"key":"1139_CR19","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.773999","volume":"13","author":"RA Hauser","year":"2022","unstructured":"Hauser RA, Barkay H, Fernandez HH, Factor SA, Jimenez-Shahed J, Gross N, et al. Long-term deutetrabenazine treatment for tardive dyskinesia is associated with sustained benefits and safety: a 3-year, open-label extension study. Front Neurol. 2022;13: 773999. https:\/\/doi.org\/10.3389\/fneur.2022.773999.","journal-title":"Front Neurol"},{"key":"1139_CR20","doi-asserted-by":"publisher","first-page":"420","DOI":"10.3389\/fphar.2020.00420","volume":"11","author":"RJ Tyson","year":"2020","unstructured":"Tyson RJ, Park CC, Powell JR, Patterson JH, Weiner D, Watkins PB, et al. Precision dosing priority criteria: drug, disease, and patient population variables. Front Pharmacol. 2020;11:420. https:\/\/doi.org\/10.3389\/fphar.2020.00420.","journal-title":"Front Pharmacol"},{"issue":"4","key":"1139_CR21","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1007\/s12325-022-02046-z","volume":"39","author":"DO Claassen","year":"2022","unstructured":"Claassen DO, Ayyagari R, Goldschmidt D, Zhou M, Leo S, Ribalov R. Defining utility values for chorea health states in patients with Huntington\u2019s disease. Adv Ther. 2022;39(4):1784\u201393. https:\/\/doi.org\/10.1007\/s12325-022-02046-z.","journal-title":"Adv Ther"},{"issue":"1","key":"1139_CR22","doi-asserted-by":"publisher","first-page":"99","DOI":"10.36469\/001c.24620","volume":"8","author":"DO Claassen","year":"2021","unstructured":"Claassen DO, DeCourcy J, Mellor J, Johnston C, Iyer RG. Impact of chorea on self-care activity, employment, and health-care resource use in patients with Huntington\u2019s disease. J Health Econ Outcomes Res. 2021;8(1):99\u2013105. https:\/\/doi.org\/10.36469\/001c.24620.","journal-title":"J Health Econ Outcomes Res"}],"container-title":["CNS Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40263-024-01139-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40263-024-01139-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40263-024-01139-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,26]],"date-time":"2025-01-26T14:53:48Z","timestamp":1737903228000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40263-024-01139-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,18]]},"references-count":22,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["1139"],"URL":"https:\/\/doi.org\/10.1007\/s40263-024-01139-3","relation":{},"ISSN":["1172-7047","1179-1934"],"issn-type":[{"value":"1172-7047","type":"print"},{"value":"1179-1934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,18]]},"assertion":[{"value":"17 November 2024","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 January 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was supported by Teva Branded Pharmaceutical Products R&D, Inc.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Samuel Frank and Claudia M. Testa served as co-principal investigators of the First-HD study. Samuel Frank was compensated for his professional role as the chair of the Data and Safety Monitoring Board for the KINECT-HD study. Jody Goldstein, Elise Kayson, Christine O\u2019Neill, and Jacquelyn Whaley report no conflicts of interest. Blair R. Leavitt is an employee of the Department of Medical Genetics and Division of Neurology, Department of Medicine, and a senior scientist at the Centre for Molecular Medicine and Therapeutics, The University of British Columbia, and BC Children\u2019s Hospital. In the last 5 years, he has held or applied for research grants in the area of neurodegenerative disease from the Canadian Institutes of Health Research, The Huntington Society of Canada, Weston Brain Foundation, Brain Canada, uniQure, Triplet Therapeutics, and the Nanomedicines Innovations Network. He has served on advisory boards for sRNAlytics, the Huntington\u2019s Disease Society of America, and the Huntington Society of Canada. In addition, he has acted as a paid consultant for Roche, uniQure, Novartis, PTC Therapeutics, Triplet Therapeutics, Genentech, Takeda, and Ionis. He is also a shareholder, co-founder, and CEO of Incisive Genetics Inc. David Oakes has received research support from Auspex (for the First-HD and related studies), Vaccinex, Prana Pharmaceuticals, Biogen, and the National Institutes of Health, and received honoraria from Raptor Pharmaceuticals and Voyager Inc. Nicholas Gross, Nayla Chaijale, Steve Barash, and Mark Forrest Gordon are employees and shareholders of Teva Pharmaceuticals.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"Consistent with the policies of the Huntington Study Group, the corresponding author is confirmed as the guarantor of the work, and all authors had full access to the data. All authors have the right to publish any and all data separate and apart from any sponsor, and we take full responsibility for the data, the analysis and interpretation, and the conduct of the research.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of Data and Material"}},{"value":"This article is based on previously conducted studies and does not contain any new studies with human participants. All involved study centers of the original trial (NCT01897896) received approval by local ethics committees and informed consent was received for all participants.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Consent was obtained during the original clinical study and no new consent forms were required\/collected for this analysis.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}},{"value":"S.F., N.C., and M.F.G. contributed to the drafting\/revision of the manuscript for content, including medical writing for content, and had a major role in the conceptualization, data curation, methodology, data analysis, supervision, validation, and reviewing. C.T., J.G., E.K., and J.W. contributed to the drafting\/revision of the manuscript for content, including medical writing for content, and had a major role in the acquisition of data and the analysis or interpretation of data. B.R.L. and C.O. had a major role in the acquisition of data. D.O., N.G., and S.B. contributed to the drafting\/revision of the manuscript for content, including medical writing for content, and the analysis or interpretation of data. All authors reviewed and approved the final manuscript.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author Contributions"}}]}}