The Cardiovascular Safety of Tumour Necrosis Factor Inhibitors in Arthritic Conditions: A Structured Review with Recommendations

Abstract

There is accumulating evidence that inflammation is a key driver of atherosclerosis development and thrombotic complications. This pathophysiological mechanism explains, at least in part, the increased cardiovascular risk of patients with immune-mediated arthritis. Experimental and clinical studies have shown that tumour necrosis factor (TNF) plays a pathological role in both vascular and joint diseases, suggesting that TNF inhibitors (TNFis) may limit cardiovascular events in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or spondyloarthritis (SpA). This review summarizes studies exploring the effects of TNFis on cardiovascular outcomes in patients with RA, PsA or SpA. Clinical studies suggest that TNFis reduce vascular inflammation and may improve (or prevent worsening of) endothelial dysfunction and arterial stiffness. There is evidence that TNFis reduce the incidence of cardiovascular events in patients with inflammatory arthritis compared with non-biological treatments, particularly in patients with rheumatoid arthritis. Fewer studies have compared the effects of different classes of biological therapy on outcomes, but found no significant difference in the risk of cardiovascular events between patients taking TNFis and other biological therapy. In contrast, patients at high cardiovascular risk may derive greater benefit from a TNFi than from a Janus kinase inhibitor (JAKi). The cardiovascular impact of JAKis is still under debate, with a recent safety warning. Targeted control of inflammation is a key strategy to reduce the risk of major adverse cardiovascular events in patients with inflammatory arthritis. Cardiovascular evaluation and risk stratification, using a multidisciplinary approach involving rheumatology and cardiology teams, are recommended to guide optimal immunomodulatory treatment.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40744-025-00753-x.

Plain Language Summary

Inflammation in blood vessel walls can lead to serious cardiovascular conditions, such as heart attacks, strokes or sudden death. Excess inflammation in autoimmune arthritic conditions like rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA) places people with these conditions at high risk of developing cardiovascular disease (CVD). Treatments for inflammatory arthritis suppress inflammation, so they may also reduce the risk of CVD. Potent anti-inflammatory drugs called biologicals (injected into the blood vessels [intravenous] or beneath the skin [subcutaneous]) are used when conventional drugs cannot control symptoms. This review evaluates research into the effects of biologicals called tumour necrosis factor inhibitors (TNFis) on CVD in people with RA, PsA or SpA. TNFis suppress some of the changes to the structure and function of blood vessels that can lead to CVD. TNFis also reduce the incidence of cardiovascular events in people with inflammatory arthritis compared with non-biological treatments, particularly in people with RA. Less is known about whether TNFis reduce the risk of CVD compared with other types of biological treatment or Janus kinase inhibitors (JAKis), but people at high cardiovascular risk may derive greater benefit from a TNFi than a JAKi. Assessing and managing cardiovascular risk is important when caring for people with inflammatory arthritis. Effective control of inflammation relieves arthritic symptoms and reduces the CVD risk. People with inflammatory arthritis and CVD may also need treatment for other cardiovascular risk factors (e.g. high blood pressure or cholesterol), requiring effective communication between different healthcare providers (e.g. rheumatologists and cardiologists).

Supplementary Information

The online version contains supplementary material available at 10.1007/s40744-025-00753-x.