Over the last 15 to 20 years, ample evidence has demonstrated that disease control in RA with methotrexate and/or TNF inhibitors is associated with a decreased risk of CV disease (CVD). The question arises as to whether the newer non-TNF biologics and targeted synthetic agents also reduce the risk of CV end points. Agents such as interleukin-6 inhibitors and Janus kinase inhibitors have mixed effects on biomarkers for CVD, producing a decrease in C-reactive protein but also increasing low-density lipoprotein cholesterol and total cholesterol. Because of this, the US Food and Drug Administration mandated a head-to-head trial comparing the effects of tocilizumab vs etanercept on CV safety. The results indicated no significant difference in the time to first major adverse CV events between agents. 

The consensus among key opinion leaders seems to be that control of RA disease activity, however you can accomplish it with any of the available drugs, will likely lessen CV risk. The one caveat is that, while there is no evidence that Janus kinase inhibitors increase the risk of myocardial infarction or stroke, there is a small but reproducible signal of increased venous thromboembolism risk; I think that most rheumatologists are screening patients for venous thromboembolism risk and that these are not the agents that people are going to gravitate to when patients are at high risk. The physiologic pathways contributing to inflammation and CVD in RA are not well understood and there may be different mechanisms in different patient populations. For example, low-dose methotrexate did not reduce inflammatory cytokines or CV events in patients with stable atherosclerosis but without RA. 

The multi-biomarker disease activity (MBDA) test is the only biomarker test that has been included in the American College of Cardiology recommendations for routine use in the clinical evaluation of patients with RA. The MBDA test appears to accurately predict CV risk in RA, and I think that it can be game changing in how we are following patients. It is a useful tool for those patients who have indeterminate presentations, such as increasing pain and fatigue but with modest tender joints and no swollen joints. Since it is challenging to know the contributing importance of comorbid factors, the MBDA test can provide reassurance regarding our clinical assessment. I often use the MBDA test during the initial evaluation to assess prognosis and therapeutic decision making, and I will also often use it when I am initiating or changing therapy. I will repeat the test to make sure that the results are in concordance with my clinical appraisal.