Does Concomitant Use of Methotrexate with JAK Inhibition Confer Benefit for Cardiovascular Outcomes? A Commentary.

IF 2.9 3区 医学 Q2 RHEUMATOLOGY Rheumatology and Therapy Pub Date : 2024-12-01 Epub Date: 2024-10-14 DOI:10.1007/s40744-024-00721-x
Peter C Taylor, Alejandro Balsa, Anne-Barbara Mongey, Mária Filková, Myriam Chebbah, Solenn Le Clanche, Linda A W Verhagen, Torsten Witte, Daniela Opris-Belinski, Hubert Marotte, Jérôme Avouac
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Abstract

This commentary explores the potential cardiovascular (CV) benefits of combining methotrexate (MTX) and Janus kinase inhibitors (JAKis) in the treatment of rheumatoid arthritis (RA). While European guidelines recommend MTX as first-line treatment, concerns about the CV risks associated with JAKis have emerged. This article reviews the existing literature to assess the role of concomitant MTX in reducing CV risk when used with JAKis. Clinical trials confirm the efficacy of JAKis in combination with MTX in terms of treatment outcomes in RA. However, the number of major adverse cardiovascular events (MACEs) reported is too low to draw conclusions on adverse CV outcomes. Indirect evidence does, however, suggest potential protective effects of MTX on CV outcomes, as several mechanisms may contribute to MTX's cardioprotective effects, including reduced inflammation, adenosine monophosphate-activated protein kinase (AMPK) activation, increased cholesterol efflux, and adenosine accumulation. These mechanisms and the available data may support the case for CV benefits of concomitant MTX when JAKis are used in the treatment of patients with RA, although further research is needed. In particular, the lipid paradox associated with RA highlights the complex relationship between RA treatments (MTX, JAKis, tumor necrosis factor (TNF) inhibitors, and interleukin (IL)-6 receptor inhibitors), inflammation, different lipid profiles, and CV risk. In the absence of contraindications and when MTX is tolerated, this commentary suggests the concomitant use of MTX and JAKis as a preferred option for optimizing CV protection in patients with RA.

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甲氨蝶呤与 JAK 抑制剂同时使用对心血管预后有益吗?评论。
这篇评论探讨了联合使用甲氨蝶呤(MTX)和Janus激酶抑制剂(JAKis)治疗类风湿性关节炎(RA)的潜在心血管(CV)益处。虽然欧洲指南推荐将MTX作为一线治疗,但与JAKis相关的心血管风险问题已引起人们的关注。本文回顾了现有文献,以评估在与 JAKis 同时使用时,MTX 在降低 CV 风险方面的作用。临床试验证实,JAKis与MTX联用可有效改善RA的治疗效果。然而,报告的主要心血管不良事件(MACE)数量太少,因此无法就心血管不良结局得出结论。不过,间接证据确实表明,MTX 对心血管预后具有潜在的保护作用,因为有几种机制可能有助于 MTX 的心脏保护作用,包括减少炎症、激活单磷酸腺苷激活蛋白激酶(AMPK)、增加胆固醇外流和腺苷积累。这些机制和现有数据可能支持在治疗 RA 患者时使用 JAKis 时同时使用 MTX 在心血管方面的益处,但仍需进一步研究。特别是,与 RA 相关的血脂悖论凸显了 RA 治疗(MTX、JAKis、肿瘤坏死因子(TNF)抑制剂和白细胞介素(IL)-6 受体抑制剂)、炎症、不同的血脂状况和 CV 风险之间的复杂关系。在没有禁忌症且能耐受 MTX 的情况下,本评论建议将同时使用 MTX 和 JAKis 作为优化 RA 患者心血管保护的首选方案。
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来源期刊
Rheumatology and Therapy
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.
期刊最新文献
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