Patients with rheumatoid arthritis (RA) treated with an immunotherapy of low-dose combination of two anticytokines have a reduced disease activity and a lower risk for cardiac events, according to researchers.
These findings are summarized in the study “Immunotherapy reduces cardiovascular risk in rheumatoid arthritis: Extra-low dose combination of two anticytokines reduces disease activity and cardiovascular events,” recently presented at Frontiers in CardioVascular Biology, a meeting organized by the European Society of Cardiology.
“Rheumatoid arthritis is an autoimmune disease in which cytokines such as tumour necrosis factor (TNF) and interferon (IFN), which normally protect the body, attack healthy cells. Patients have painful and inflamed joints. They are also at increased cardiovascular risk, particularly if their rheumatoid arthritis is not controlled,” Prof. Aida Babaeva, head of the Department of Internal Medicine at Volgograd State Medical University, Russia, said in a news release.
Immunotherapy is based on drugs that act on our immune system, either by inducing, enhancing, or suppressing an immune response. Tumor necrosis factor-alpha (TNF-alpha), for example, is a proinflammatory cytokine that plays a pivotal role in regulating inflammatory responses in rheumatoid arthritis. Targeting this cytokine, along with other cytokines, may prove beneficial in RA patients.
Babaeva’s previous research has showed that anticytokine-based therapy reduced RA disease activity. Specifically, extra-low doses of anti-TNF alpha reduced the levels of several key players in inflammation (C-reactive protein, rheumatoid factor, TNF, interleukin-1, and interleukin-6). The benefits were more pronounced when combined with anti-interferon (IFN) gamma, both at extra-low doses.
Now, researchers investigated how the previous treatments affected RA patients’ cardiovascular risks. Rheumatoid arthritis is associated with dysfunction of the blood vessel lining, called the endothelium. This results in severe damages, including lipid accumulation in the artery wall, plaque formation, and atherosclerosis. Pro-coagulant state (an abnormally increased tendency toward blood clotting and thrombosis) is also associated with increased RA disease activity.
A total of 68 patients who had suffered from active rheumatoid arthritis for at least five years were enrolled in the study and randomly assigned to receive either immune therapy (anti-TNF alpha and anti-IFN gamma) together with standard disease-modifying therapy (38 patients), or a placebo plus standard therapy (30 patients).
Patients were monitored over three years for rheumatoid arthritis disease activity and cardiovascular events. Those treated with combined immunotherapy and standard therapy showed lower disease activity scores when compared to the placebo controls.
The incidence of cardiovascular events (including unstable angina, severe hypertensive crisis, and deterioration of chronic heart failure) was also significantly reduced: only 13 percent of patients on the combined anticytokines therapy, compared to 37 percent of patients on conventional disease-modifying drugs alone.
“Our findings suggest that the decreased rheumatoid arthritis disease activity with the combination of anticytokines translates into decreased cardiovascular risk,” Babaeva said. “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.”
A total of 71% of RA patients suffering from hypertension and treated with the immunotherapy reached normal blood pressure levels compared to 32% in those treated with standard therapy alone.
“This doesn’t mean that the two drugs directly impact on blood pressure. But the combination can improve endothelial function and it could be that blood pressure is more stable when disease activity is low,” Babaeva said.
In fact, the researchers believe “the combination of two anticytokines containing extra-low doses of antibodies against TNF alpha and IFN gamma can improve the efficacy of standard rheumatoid arthritis therapy and decrease cardiovascular risk.”
“We do not think that all patients with rheumatoid arthritis should be treated with this combination. 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),” Babaeva said.
“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,” she added.