FDA monitoring heart failure in patients taking infliximab or etanercept

[Guest guest]

Oct 29, 2002

FDA monitoring heart failure in patients taking infliximab or etanercept

New Orleans, LA - Food and Drug Administration (FDA) investigators have

identified 42 cases of new heart failure and 9 cases of heart failure

exacerbation in patients taking either etanercept (n=30) or infliximab

(n=21). Ten of these cases were new-onset heart failure in patients younger

than 50. Dr Hyon J. Kwon (FDA's Center for Biologics Evaluation and Research

[CBER]) discussed these cases at a standing-room-only session on safety

issues, with the result that physicians in the audience came forward with 2

more previously unreported cases of heart failure associated with anti-TNFa

treatment.

" Our analysis is based on postmarketing FDA surveillance data on infliximab

and etanercept, " Kwon said. " We, like others, had expected that blocking

TNFa might be helpful in heart failure, since increased levels of TNFa lead

to heart dysfunction in animal studies. After the phase 2 trial of

infliximab for heart failure showed higher mortality and more

hospitalizations for worsening of heart failure, we decided to analyze

reports of heart failure in the FDA's MedWatch Adverse Event Reporting

System (AERS) database. "

AERS data are mainly a warning of possible problems, as reports are

voluntary and physician initiated, not the product of comprehensive surveys

of patients taking a specific drug. They are thus likely to be

underestimates of the problems actually occurring in the community.

Kwon's group searched MedWatch for patients with either a new onset of heart

failure or a worsening of preexisting heart failure after taking a TNFa

antagonist. They found 51 cases. The median age of these patients was 64

years (range 19 to 87 years), and 53% were female.

Kwon said that teasing out the contribution of anti-TNFa drugs to the heart

failure events was difficult because most patients were in their 60s or 70s

when they developed heart failure, at which point numerous confounding

variables associated with aging had come into play. To work around this

problem, Kwon pulled out the data on all patients younger than 50 and

recontacted their physicians to collect information on predisposing factors,

clinical course, and final outcome.

Six of these younger patients had taken infliximab; 4 had taken etanercept.

Echocardiography data for 9 of 10 showed median ejection fraction of 20%.

Three of 10 had preexisting risk factors for heart failure such as

hypertension, diabetes, or pulmonary disease.

All 10 patients discontinued anti-TNFa treatment when heart failure was

diagnosed. Three had complete resolution of heart failure symptoms, but one

died, and 6 had only partial improvement with traditional heart failure

treatment.

" This is the first case series of new-onset heart failure in patients who

have taken TNF antagonists. These cases are a signal that there is a

possible association of heart failure with these drugs, and given the limits

of the AERS voluntary reporting system, we suspect that there are probably

many more unreported cases. Clinicians should be aware that TNF antagonists

might induce new-onset heart failure or exacerbate existing disease, " Kwon

concluded.