BERLIN, Feb. 28 -- In patients with rheumatoid arthritis, treatment with a tumor necrosis factor-alpha inhibitor does not appear to increase the risk of heart failure or worsen existing disease, a large patient registry has suggested.
In a study to examine the interrelationships of TNF-a inhibition, RA, and heart failure, Joachim Listing, Ph.D., of the German Rheumatism Research Center, and colleagues found that irrespective of treatment a higher RA disease activity score after three years of follow-up predicted a significantly increased risk of heart failure (P=0.019).
Although TNF-a inhibition was associated with a non-significant residual heart failure risk, it was offset by the treatment's favorable effect on arthritis disease activity, the investigators reported in the March issue of Arthritis & Rheumatism. An analysis limited to baseline characteristics revealed a non-significant 30% decrease in heart failure risk in patients treated with TNF-a inhibitors.
"The findings of this study indicate that TNF-a inhibitor treatment that effectively reduces the inflammatory activity of RA is more likely to be beneficial than harmful with regard to the risk of heart failure . . . , " the authors concluded. "Furthermore, the data suggest that TNF-a inhibition does not increase the risk of worsening of prevalent heart failure."
Inflammation, joint destruction, and loss of function are hallmark characteristics of rheumatoid arthritis. The inflammatory cytokine TNF-a contributes to the pathogenesis of rheumatoid arthritis, the authors noted.
TNF-alpha also mediates endothelial dysfunction, vascular instability, and disease progression in atherosclerosis, they continued. Additionally, TNF-a plays a role in the progression of heart failure.
Treatment with inhibitors of TNF-a significantly reduces the signs and symptoms of rheumatoid arthritis. However, the same inhibitors failed to demonstrate a positive effect on severe heart failure, and some clinical trial data suggested an increased heart failure risk with TNF-alpha inhibition compared with placebo.
Dr. Listing and colleagues reviewed data from the German biologics registry. Known by the acronym RABBIT, the registry is an ongoing prospective cohort study of heart failure risk factors in patients with rheumatoid arthritis.
The authors reported findings from an analysis of 2,757 patients treated with a TNF-a inhibitor and 1,491 treated with conventional disease-modifying drugs (DEMARDs) at the time of enrollment in the registry. Cox proportional hazards models were used to examine the influence of disease- and treatment-related factors on new or worsening heart failure.
The three-year rate of heart failure was 2.2% in patients with existing cardiovascular disease at baseline and 0.4% in those without. After adjustment for conventional cardiovascular risk factors, a higher score on the 28-joint disease activity scale significantly increased the risk of developing heart failure (HR 1.47, 95% CI 1.07 to 2.02).
Anti-TNF therapy tended to be associated with an increased risk of heart failure versus conventional disease-modifying drugs. Multivariate analysis yielded a hazard ratio of 1.66 for TNF-a inhibitors compared with conventional drugs, but the difference was not significant (95% CI 0.67 to 4.10, P=0.28).
In a simplified multivariate regression model that combined the positive and negative effects of anti-TNF therapy, the hazard ratio tilted in favor of the TNF-a inhibitors, although the difference did not reach significance (HR 0.70, 95% CI 0.27 to 1.84, P=0.47).
The analysis also revealed evidence of an increased heart failure hazard associated with use of glucocorticoids or Cox-2 inhibitors, which might dilute the favorable effects of TNF-alpha inhibitors.
"In addition to the degree of activity of the rheumatic disease, low functional capacity was found to be a significant predictor of heart failure," the authors wrote.
"Our data therefore suggest that controlling the inflammatory activity of RA not only leads to a better outcome of the rheumatic disorder, but also contributes to a reduction of cardiovascular risk."
Dr. Listing had no disclosures, but coauthor Siegfried Wassenberg, M.D., disclosed consulting fees and honoraria received from Abbott, Wyeth, Roche, and Bristol-Myers Squibb.
Primary source: Arthritis & Rheumatism
Source reference:
Listing J, et al "Does tumor necrosis factor α inkhibition promote or prevent heart failure in patients with rheumatoid arthritis?" Arthritis Rheum 2008; 58: 667-677
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