IF 2.9
3区 医学
Q2 RHEUMATOLOGY
引用次数: 0
摘要
简介：Lorecivivint（LOR）是一种CDC样激酶/双特异性酪氨酸激酶（CLK/DYRK）抑制剂，被认为可调节炎症和Wnt通路，目前正被开发为一种潜在的关节内膝关节骨关节炎（OA）治疗药物。本试验的目的是在两项二期试验的观察性延长期内评估 LOR 的长期安全性：这项为期 60 个月的观察性延伸研究（NCT02951026）是一项为期 12 个月的 2a 期试验（NCT02536833）和为期 6 个月的 2b 期试验（NCT03122860）的延伸，由于数据推断有限，该研究在 36 个月后以行政方式结束。参试者在母试验基线接受单次关节内注射 LOR 或安慰剂 (PBO)。主要结果是严重不良事件（SAEs）的发生率比较，次要结果是AEs和类似的安全性指标。在单侧膝关节疼痛和广泛疼痛程度低到足以让参与者区分其目标膝关节疼痛的亚人群中，通过事后基线调整的协方差分析（ANCOVA）比较了LOR 0.07 mg组和PBO组在西安大略和麦克马斯特大学骨关节炎指数（WOMAC）疼痛和功能子评分以及内侧关节间隙宽度（JSW）方面与基线相比的变化：延伸研究的安全性分析组包括495名接受过LOR治疗的参与者和208名对照组参与者，在研究结束时分别有409人（82.6%）和175人（84.1%）仍在接受治疗。38名患者（5.4%）共报告了68例SAE，研究人员认为这些SAE均与治疗无关。各组的 AE 发生率相似。在事后的亚组疗效分析中，与PBO相比，LOR 0.07 mg在注射后12个月内的WOMAC疼痛和功能评分与基线相比平均改善幅度更大。18个月后，内侧JSW没有观察到组间差异：结论：LOR总体看来安全且耐受性良好。临床试验注册号：NCT02951026：临床试验注册号：NCT02951026。本文章由计算机程序翻译，如有差异，请以英文原文为准。
Evaluation of Safety and Efficacy of a Single Lorecivivint Injection in Patients with Knee Osteoarthritis: A Multicenter, Observational Extension Trial.
Introduction: Lorecivivint (LOR), a CDC-like kinase/dual-specificity tyrosine kinase (CLK/DYRK) inhibitor thought to modulate inflammatory and Wnt pathways, is being developed as a potential intra-articular knee osteoarthritis (OA) treatment. The objective of this trial was to evaluate long-term safety of LOR within an observational extension of two phase 2 trials.
Methods: This 60-month, observational extension study (NCT02951026) of a 12-month phase 2a trial (NCT02536833) and 6-month phase 2b trial (NCT03122860) was administratively closed after 36 months as data inferences became limited. Participants received a single intra-articular LOR or placebo (PBO) injection at their parent-trial baseline. The primary outcome was the comparative incidence of serious adverse events (SAEs), with AEs and similar safety measures comprising secondary outcomes. A post hoc baseline-adjusted analysis of covariance (ANCOVA) compared changes from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Function subscores and medial joint space width (JSW) between LOR 0.07 mg and PBO groups in a subpopulation of participants with unilateral knee pain and widespread pain low enough to allow participants to differentiate their target knee pain.
Results: The safety analysis set for the extension study included 495 LOR-treated and 208 control participants, with 409 (82.6%) and 175 (84.1%) remaining at study close, respectively. There were 68 SAEs reported in 38 (5.4%) patients; none were considered treatment-related by investigators. The incidence of AEs was similar between groups. In the post hoc subgroup efficacy analyses, LOR 0.07 mg demonstrated greater mean improvements from baseline compared with PBO in WOMAC pain and function scores out to 12 months post-injection. No between-group differences in medial JSW were observed out to 18 months.
Conclusions: LOR appeared generally safe and well tolerated. Efficacy analyses on the subset of completer patients demonstrated durable symptom improvements in WOMAC pain and function for at least 12 months compared to PBO after a single injection of LOR.
Clinical trial registration number: NCT02951026.
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来源期刊
Rheumatology and Therapy
RHEUMATOLOGY-
CiteScore
6.00
自引率
5.30%
发文量
91
审稿时长
6 weeks
期刊介绍：
Aims and Scope
Rheumatology 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 rheumatologic therapies. Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed.
Areas of focus include, but are not limited to, rheumatoid arthritis, gout, gouty arthritis, psoriatic arthritis, osteoarthritis, juvenile idiopathic/rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis, Pompe’s disease, inflammatory joint conditions, musculoskeletal conditions, systemic sclerosis, and fibromyalgia.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial protocols, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Rheumatology 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.
Ethics and Disclosures
The journal is a member of the Committee on Publication Ethics (COPE) and subscribes to its principles on how to deal with acts of misconduct thereby committing to investigate allegations of misconduct in order to ensure the integrity of research. Content in this journal is peer-reviewed (Single-blind). For more information on our publishing ethics policies, please see here: https://www.springer.com/gp/editorial-policies
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, allowing the advancement of rheumatologic therapies.
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, GPP 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
Rheumatology 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:
https://springerhealthcare.com/expertise/publishing-digital-features/
Preprints
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. Authors should disclose details of preprint posting during the submission process or at any other point during consideration in the journal. Once the manuscript is published, it is the author''s responsibility to ensure that the preprint record is updated with a publication reference, including the DOI and a URL link to the published version of the article on the journal website.
Please see here for further information on preprint sharing: https://www.springer.com/gp/authors-editors/journal-author/journal-author-helpdesk/submission/1302#c16721550
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. Where reviewer recommendations are conflicted, the editorial board 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.
Considering the time and effort required for a detailed peer review we reward our regular reviewers with the opportunity to publish without publication fees (pending peer review) for every three reviews completed per calendar year.
Copyright
Rheumatology 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.
Publication Fees
Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of €5,250/$6,000/£4,300. The journal will consider fee discounts and waivers for developing countries and this is decided on a case-by-case basis.
Open Access
All articles published by Rheumatology and Therapy are published open access.
Contact
For more information about the journal, including pre-submission enquiries, please contact charlotte.maddocks@springernature.com.
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