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-

CiteScore

6.00

自引率

5.30%

发文量

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. 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