Department of Propedeutics of Internal Medicine, Faculty of Medicine, Medical University - Varna, 9002, Varna, Bulgaria.
Clinic of Rheumatology, University Hospital St. Marina - Varna, 9010, Varna, Bulgaria.
Clin Rheumatol. 2023 Oct;42(10):2651-2676. doi: 10.1007/s10067-023-06587-8. Epub 2023 Mar 30.
Rheumatoid arthritis (RA) increases the risk of cardiovascular disease (CVD), with inflammation playing a key role. Biologic and targeted synthetic drugs used to treat RA can induce systemic immunomodulation and may have pleiotropic effects on vascular function, making it crucial to investigate their impact on CVD risk in RA patients.
A systematic review of the literature was conducted to investigate the impact of biologic and targeted synthetic treatments approved for RA on various cardiovascular markers, including endothelial function, arterial stiffness, and subclinical atherosclerosis. Our analysis included a search of the MedLine (via PubMed) and Web of Science databases using a pre-determined search strategy. We conducted a narrative synthesis of the included studies due to heterogeneity in study design and outcome measures.
From an initial pool of 647 records, we excluded 327 studies based on their titles and abstracts, and we selected 182 studies for final examination. Ultimately, 58 articles met our inclusion criteria and were included in our systematic review. Our analysis of these studies revealed a positive effect of biologic and targeted synthetic therapies on vascular dysfunction associated with RA. However, the impact of these treatments on subclinical atherosclerosis was inconsistent.
Overall, our systematic review provides important insights into the potential cardiovascular benefits of biologic and targeted synthetic treatments for RA by a still unknown mechanism. These findings can inform clinical practice and contribute to our understanding of their possible effects on early vascular pathology. Key Points • Great heterogeneity of methods are used to evaluate the endothelial function and arterial stiffness in patients with RA on biologic and targeted synthetic antirheumatic drugs. • Most studies have shown a considerable improvement in endothelial function and arterial stiffness with TNFi, despite some studies reporting only transient or no improvement. • Anakinra and tocilizumab may have a beneficial effect on vascular function and endothelial injury, as indicated by increased FMD, coronary flow reserve, and reduced levels of biomarkers of endothelial function, while the overall impact of JAKi and rituximab remains inconclusive based on the reviewed studies. • To fully comprehend the distinctions between biologic therapies, more long-term, well-designed clinical trials are necessary using a homogeneous methodology.
类风湿关节炎（RA）增加了心血管疾病（CVD）的风险，炎症在其中起着关键作用。用于治疗 RA 的生物制剂和靶向合成药物可诱导全身免疫调节，并可能对血管功能产生多效性影响，因此研究它们对 RA 患者 CVD 风险的影响至关重要。
系统检索了文献，以研究批准用于 RA 的生物制剂和靶向合成治疗对各种心血管标志物的影响，包括内皮功能、动脉僵硬度和亚临床动脉粥样硬化。我们的分析包括使用预先确定的搜索策略在 MedLine（通过 PubMed）和 Web of Science 数据库中进行搜索。由于研究设计和结局测量的异质性，我们对纳入的研究进行了叙述性综合。
从最初的 647 条记录中，我们根据标题和摘要排除了 327 项研究，并选择了 182 项研究进行最终检查。最终，有 58 篇文章符合我们的纳入标准，并纳入了我们的系统评价。我们对这些研究的分析表明，生物制剂和靶向合成疗法对与 RA 相关的血管功能障碍有积极影响。然而，这些治疗对亚临床动脉粥样硬化的影响不一致。
总的来说，我们的系统评价通过一种未知的机制，为生物制剂和靶向合成治疗 RA 的潜在心血管益处提供了重要的见解。这些发现可以为临床实践提供信息，并有助于我们了解它们对早期血管病理学的可能影响。
• 用于评估生物制剂和靶向合成抗风湿药物治疗的 RA 患者内皮功能和动脉僵硬度的方法存在很大的异质性。
• 大多数研究表明 TNFi 可显著改善内皮功能和动脉僵硬度，但有些研究仅报告短暂或无改善。
• 阿那白滞素和托珠单抗可能对血管功能和内皮损伤有有益的影响，表现为 FMD、冠状动脉血流储备增加和内皮功能生物标志物水平降低，而依那西普和利妥昔单抗的总体影响基于综述研究仍不确定。
• 为了充分理解生物疗法之间的区别，需要使用同质的方法进行更多长期、精心设计的临床试验。
