SELECTED ARTICLES FROM THE RECENT LITERATURE 2003

9/18/03

Heart failure during treatment with tumor necrosis factor antagonists

Summary
Treatment with antagonists of tumor necrosis factor (TNF-ant) is now being used extensively in the management of Crohn's disease and some other conditions. Currently approved TNF-ant agents are infliximab, an anti-TNF antibody, and etanercept, a competitive antagonist of TNF. Kwon et al of the FDA have described 47 reports to their agency of individuals who manifested new (n=38) or worsening (n=9) congestive heart failure (CHF) during TNF-ant therapy. In the 38 patients with new onset CHF, 19 had no other identifiable risk factors; 10 individuals were less than 50 years old. After TNF-ant therapy was discontinued and CHF therapy was started in 10 of these patients, the CHF remitted in 3 individuals and improved in 6. One patient died. The authors concluded that TNF-ant therapy might induce new onset CHF or aggravate pre-existent CHF in a small percentage of treated individuals.

Reference
Intern Med 2003;138:807-11

Editor’s Comments
Since this article was a description of case reports to the FDA without an appropriate control group for comparison, one cannot draw any firm conclusions about a causal role of the TNF-ant therapy in the CHF observed in the reported patients. However, the fact that no other risk factors for CHF were present in 50% of the new onset CHF cases (and the relatively young age of some patients) certainly raises a suspicion that CHF may be a rare complication of TNF-ant therapy. If indeed a causal relationship is present, the underlying mechanism has not been identified.

I have reviewed this article for the AADMC because a trial of the use of TNF-ant therapy in severe asthma has been recently reported. Although no adverse cardiac effects were noted in this report, the study groups were too small to detect what may be a very infrequent complication. Of note, other reports have described occasional cases of pulmonary tuberculosis (TB) in individuals treated with TNF-ant agents. Such individuals have generally had histories of TB in the past or in family members.


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