Immunotherapy reduces cardiovascular risk in rheumatoid arthritis

Extra-low dose combinat ion of two anticytokines reduces disease activity and cardiovascular events Immunotherapy reduces cardiovascular risk in patients with rheumatoid arthritis, according to research presented by Professor Aida Babaeva, head of the Department of Internal Medicine, Volgograd State Medical University, Volgograd, Russia. The combination of two extralow dose anticytokine drugs reduced rheumatoid arthritis disease activity and cardiovascular events.
‘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,’ said Professor Babaeva. ‘Patients have painful and inflamed joints. They are also at increased cardiovascular risk, particularly if their rheumatoid arthritis is not controlled.’
Professor Babaeva’s previous research showed that treatment with anticytokine drugs can decrease the activity of rheumatoid arthritis. Extra-low dose anti-TNFα reduced levels of inflammatory mediators and cytokines including C-reactive protein (CRP), rheumatoid factor, TNF, interleukin-1 (IL-1), and interleukin-6 (IL-6). The effect was more apparent and developed earlier when patients were treated with a combination of anti-TNFα and anti-IFNγ both at extra-low doses.
The current study investigated the impact of the combination of drugs on cardiovascular events. It included 68 patients who had suffered from active rheumatoid arthritis for at least five years. Patients were randomized to receive the combination of anti-TNFα and anti-IFNγ plus standard disease-modifying therapy (38 patients) or placebo plus standard therapy (30 patients). During the three year follow up period the investigators monitored rheumatoid arthritis disease activity and cardiovascular events.
Patients taking the combination of anticytokines had a lower rheumatoid arthritis disease activity score, as measured by the DAS28,2 and more dramatic decreases in IL-1, IL-6 and TNFα than the group on standard therapy alone.
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 (37percent) compared to those also taking the combination of anticytokines (13percent).
Professor Babaeva said: ‘Our findings suggest that the decreased  rheumatoid arthritis disease activity with the combination of anticytokines translates into decreased cardiovascular risk. 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 example, rheumatoid arthritis is associated with dysfunction of the blood  vessel lining (called endothelium), which leads to lipid accumulation in the artery wall, plaque formation and atherosclerosis. Increased disease activity is also linked with a pro-coagulant 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.
In patients with hypertension, target blood pressure was reached in 71percent of those taking the combination of anticytokines compared to just 32percent of patients on standard therapy alone.
Professor Babaeva said: ‘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.’
‘We found that the combination of two anticytokines containing extra-low doses of antibodies against TNFα and IFNγ can improve the efficacy of standard rheumatoid arthritis therapy and decrease cardiovascular risk,’ said Professor Babaeva.

European Society of Cardiology