Russian scientists have presented data that shows immunotherapy can reduce the risk of cardiovascular events in patients with rheumatoid arthritis. The investigators found that the combination of two extra-low-dose anti-cytokine drugs decreased rheumatoid arthritis disease activity and cardiovascular, cardiac disease activity. The findings from this study were presented over the weekend at the 2016 Frontiers in CardioVascular Biology (FCVB) conference under the title “Cardiovascular Risk Modifying with Extra-Low Dose Anti-Cytokine Drugs in Rheumatoid Arthritis.”
“Rheumatoid arthritis is an autoimmune disease in which cytokines such as tumor necrosis factor (TNF) and interferon (IFN), which normally protect the body, attack healthy cells,” explained Aida Babaeva, M.D., head of the department of internal medicine at Volgograd State Medical University, Russia. “Patients have painful and inflamed joints. They are also at increased cardiovascular risk, particularly if their rheumatoid arthritis is not controlled.”
The research team observed the impact of combination drugs on cardiovascular events. The study included 68 patients who had suffered from active rheumatoid arthritis for at least 5 years. Patients were randomized to receive the combination of anti-TNF-α and anti-IFN-γ, plus standard disease-modifying therapy (38 patients) or placebo plus standard therapy (30 patients). During the 3-year follow-up period, the investigators monitored rheumatoid arthritis disease activity and cardiovascular events.
The investigators found that patients taking the combination of anti-cytokines had a lower rheumatoid arthritis disease activity score and more dramatic decreases in cytokines IL-1, IL-6, and TNF-α than the group on standard therapy alone. Moreover, the incidence of cardiovascular events (unstable angina, severe hypertensive crisis, and deterioration of chronic heart failure) was more than double in the group on conventional disease-modifying drugs alone (37%) compared to those also taking the combination of anti-cytokines (13%).
“Our findings suggest that the decreased rheumatoid arthritis disease activity with the combination of anti-cytokines translates into decreased cardiovascular risk,” Dr. Babaeva noted. “Rheumatoid arthritis promotes the development of cardiovascular disease in a number of ways. Therefore, decreasing disease activity may also reduce cardiovascular risk by slowing down or halting these processes.”
For instance, rheumatoid arthritis is associated with dysfunction of the endothelium, which leads to lipid accumulation in the artery wall, plaque formation, and atherosclerosis. Increased disease activity has also been linked with a procoagulant state in which patients are more prone to blood clots and thrombosis. Patients with active disease have an increase in molecules that promote inflammation, which has been associated with an increased risk of cardiovascular disease.
Interestingly, the Russian scientists found that in patients with hypertension, target blood pressure was reached in 71% of those taking the combination of anti-cytokines compared to just 32% of patients on standard therapy alone.
“This doesn't mean that the two drugs directly impact on blood pressure,” Dr. Babaeva remarked. “But the combination can improve endothelial function, and it could be that blood pressure is more stable when disease activity is low. We found that the combination of two anti-cytokines containing extra-low doses of antibodies against TNF-α and IFN-γ could improve the efficacy of standard rheumatoid arthritis therapy and decrease cardiovascular risk.”
Dr. Babaeva went on to conclude that “we do not think that all patients with rheumatoid arthritis should be treated with this combination, yet in patients with highly active disease, the standard biologics are better at preventing severe complications such as progressive joint destruction and/or systemic manifestations (vasculitis, uveitis, involvement of internal organs). We recommend this new approach for preventing cardiovascular events in patients with moderate disease activity who are not receiving the standard biologics and who do not have severe complications.”