Samuel Frank, Karen E Anderson, Hubert H Fernandez, Robert A Hauser, Daniel O Claassen, David Stamler, Stewart A Factor, Joohi Jimenez-Shahed, Hadas Barkay, Amanda Wilhelm, Jessica K Alexander, Nayla Chaijale, Steve Barash, Juha-Matti Savola, Mark Forrest Gordon, Maria Chen
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For HD, safety data were integrated from the 12-week pivotal study (First-HD) and through week 15 of the OLE study (ARC-HD) for patients previously receiving placebo. Integrated deutetrabenazine data were compared with placebo from the pivotal study.</p><p><strong>Results: </strong>For TD, deutetrabenazine (n = 384) was generally well tolerated compared with placebo (n = 130). Adverse event (AE) incidence was numerically higher in the response-driven deutetrabenazine vs the fixed-dose deutetrabenazine and placebo groups, respectively (any AE, 59.5% vs 44.4-50.0% and 53.8%; treatment-related AE, 38.1% vs 18.1-25.0% and 30.8%). Serious AEs were reported for 2.8-8.3% of patients in the deutetrabenazine groups and 6.9% in the placebo group. Common AEs (≥ 4%) included headache, somnolence, nausea, anxiety, fatigue, dry mouth, and diarrhea. AE incidence was higher during the titration vs maintenance periods. For HD, AE incidence was numerically higher with deutetrabenazine (n = 84) vs placebo (n = 45; any AE, 64.3% vs 60.0%; treatment-related AE, 38.1% vs 26.7%); serious AEs were reported for similar proportions for the deutetrabenazine and placebo groups, 2.4% and 2.2%, respectively. 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引用次数: 0
摘要
简介去甲替拉嗪是一种囊泡单胺转运体2抑制剂，用于治疗与亨廷顿病（HD）相关的迟发性运动障碍（TD）和舞蹈症。为了加强对单个试验安全性信号的检测，我们对脱乙酰丙嗪治疗TD和HD舞蹈症的安全性进行了综合分析：对于TD，整合了两项为期12周的关键性研究（ARM-TD和AIM-TD）以及开放标签延伸（OLE）研究（RIM-TD）第15周的安全性数据。数据按照去甲替拉嗪治疗组和安慰剂组进行分析。对于 HD，则整合了 12 周关键研究（First-HD）和 OLE 研究（ARC-HD）第 15 周的安全性数据，这些数据针对的是之前接受过安慰剂治疗的患者。整合后的杜替拉嗪数据与关键研究中的安慰剂数据进行了比较：对于TD，与安慰剂（n = 130）相比，去乙酰丙嗪（n = 384）的耐受性普遍良好。反应驱动的去替拉嗪组与固定剂量的去替拉嗪组和安慰剂组相比，不良事件（AE）发生率在数量上分别更高（任何AE，59.5% vs 44.4-50.0% 和53.8%；治疗相关AE，38.1% vs 18.1-25.0% 和30.8%）。在去甲替拉嗪组和安慰剂组中，分别有2.8%-8.3%和6.9%的患者出现严重AE。常见的不良反应（≥ 4%）包括头痛、嗜睡、恶心、焦虑、疲劳、口干和腹泻。滴定期与维持期的 AE 发生率更高。对于HD，去乙酰丙嗪组（n = 84）与安慰剂组（n = 45；任何AE，64.3% vs 60.0%；治疗相关AE，38.1% vs 26.7%）相比，AE发生率更高；去乙酰丙嗪组与安慰剂组报告的严重AE比例相似，分别为2.4%和2.2%。常见的不良反应（≥4%）包括烦躁、跌倒、抑郁、口干和疲劳：对TD研究的综合分析数据和对HD舞蹈症研究的综合分析数据显示，去甲替拉嗪具有良好的安全性，在各适应症中的耐受性良好：试验注册：ClinicalTrials.gov标识符：NCT02291861、NCT02195700、NCT01795859、NCT02198794、NCT01897896。
Safety of Deutetrabenazine for the Treatment of Tardive Dyskinesia and Chorea Associated with Huntington Disease.
Introduction: Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor used to treat tardive dyskinesia (TD) and chorea associated with Huntington disease (HD). To enhance detection of safety signals across individual trials, integrated safety analyses of deutetrabenazine in TD and HD chorea were conducted.
Methods: For TD, safety data were integrated from two 12-week pivotal studies (ARM-TD and AIM-TD) and through week 15 of the open-label extension (OLE) study (RIM-TD). Data were analyzed by deutetrabenazine treatment group and placebo. For HD, safety data were integrated from the 12-week pivotal study (First-HD) and through week 15 of the OLE study (ARC-HD) for patients previously receiving placebo. Integrated deutetrabenazine data were compared with placebo from the pivotal study.
Results: For TD, deutetrabenazine (n = 384) was generally well tolerated compared with placebo (n = 130). Adverse event (AE) incidence was numerically higher in the response-driven deutetrabenazine vs the fixed-dose deutetrabenazine and placebo groups, respectively (any AE, 59.5% vs 44.4-50.0% and 53.8%; treatment-related AE, 38.1% vs 18.1-25.0% and 30.8%). Serious AEs were reported for 2.8-8.3% of patients in the deutetrabenazine groups and 6.9% in the placebo group. Common AEs (≥ 4%) included headache, somnolence, nausea, anxiety, fatigue, dry mouth, and diarrhea. AE incidence was higher during the titration vs maintenance periods. For HD, AE incidence was numerically higher with deutetrabenazine (n = 84) vs placebo (n = 45; any AE, 64.3% vs 60.0%; treatment-related AE, 38.1% vs 26.7%); serious AEs were reported for similar proportions for the deutetrabenazine and placebo groups, 2.4% and 2.2%, respectively. Common AEs (≥ 4%) included irritability, fall, depression, dry mouth, and fatigue.
Conclusions: Data from an integrated analysis of studies in TD and an integrated analysis of studies of chorea in HD showed that deutetrabenazine has a favorable safety profile and is well tolerated across indications.
期刊介绍：
Aims and Scope
Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice.
Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial designs, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Neurology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
Rapid Publication
The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted, it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model, this allows for the rapid and efficient communication of the latest research and reviews to support scientific discovery and clinical practice.
Open Access
All articles published by Neurology and Therapy are open access.
Personal Service
The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning that authors will always have a personal point of contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. We also encourage pre-submission enquiries and are always happy to provide a confidential assessment of manuscripts.
Digital Features and Plain Language Summaries
Neurology and Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’.
For examples of digital features please visit our showcase page https://springerhealthcare.com/expertise/publishing-digital-features/
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Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of €5250/$6000/£4300. The journal will consider fee discounts and waivers for developing countries and this is decided on a case-by-case basis.
Peer Review Process
Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria.
At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials and Letters which are generally reviewed by one member of the Editorial Board. Where reviews conflict, an Editorial Board Member will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed. Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised, it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case-by-case basis and should be sent to the journal editor, and authors are welcome to make rebuttals against individual reviewer comments, if appropriate.
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We encourage posting of preprints of primary research manuscripts on preprint servers, authors'' or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals.
Please see here for further information on preprint sharing: https://www.springer.com/gp/authors-editors/journal-author/journal-author-helpdesk/submission/1302#c16721550
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Neurology and Therapy is published under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0.
Contact
For more information about the journal, including pre-submission enquiries, please contact managing editor Lydia Alborn at lydia.alborn@springer.com.
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