Infliximab Therapy Associated With Reactivation Tuberculosis

October 13, 2001

http://orthopedics.medscape.com/reuters/prof/2001/10/10.11/20011010clin004.html

WESTPORT, CT (Reuters Health) Oct 10 - Active tuberculosis may develop

soon after initiation of treatment with infliximab, according to a

report in the New England Journal of Medicine for October 11. " Before

starting patients on infliximab, physicians should make every attempt to

make sure that the person is not infected with TB, " lead author Dr.

ph Keane, a TB specialist at Boston University School of Medicine,

told Reuters Health.

Dr. Keane and colleagues analyzed reports from the US Food and Drug

Administration's Adverse Event Reporting System (AERS). Seventy patients

were reported to have TB within 1 to 52 weeks after starting treatment

with infliximab, an antibody against tumor necrosis factor-alpha that is

used in the treatment of Crohn's disease and rheumatoid arthritis.

The investigators note that other serious opportunistic infections have

been associated with this drug, but the frequency of TB exceeds that

associated with other infections. In addition, " infliximab currently

leads all other drugs and biologic products with respect to the number

of cases of tuberculosis reported to the AERS, " according to the report.

Based on the reports he analyzed, Dr. Keane described the type of TB

that infliximab-treated patients developed as " sinister. " More than half

had extrapulmonary TB and nearly a quarter developed disseminated

infection. Of the 12 patients who died, at least four succumbed as a

direct result of the TB. The investigators believe that most of the

patients had reactivation disease, based on the older age of the

patients, the low number with recent exposure to TB, and the low

incidence of TB in the countries where the patients lived.

Before prescribing infliximab, " it's extremely important to ask patients

if they've had a positive skin test in the past, " Dr. Keane emphasized.

" If they did, ask if they took isoniazid for 9 months. " Other questions

he said physicians should ask are whether the patient has ever been

exposed to a person with TB, or ever lived in a country such as India or

one of the many African countries where TB is highly prevalent.

Dr. Keane recommended that if a skin test shows the patient is infected,

isoniazid treatment should be initiated at the same time as infliximab.

When prescribing infliximab, physicians should counsel patients about

symptoms that might suggest tuberculosis and the need to seek medical

attention if such symptoms appear.

There may actually be a bright side to the finding that infliximab

therapy increases the risk of TB, Dr. Keane pointed out. He explained

that scientists working with cells and with mice know that tumor

necrosis factor (TNF) is important in the immune response to TB, but up

until now, they have seen no evidence of TNF's influence on TB in human

beings. " So we were being laughed out of court every time we talked

about it, " he grumbled. " 'You're looking at mice; who cares about mice?'

'That may be important for Mickey Mouse, but it's not important for my

patients,' other physicians would say. "

Observing infliximab's ability to reactivate TB " confirms that TNF is

important in TB, " Dr. Keane said. " Maybe someday we can use that

information to rescue patients who are losing their battle with TB by

supporting TNF. Perhaps we could even use this information to design a

better vaccine. " " Perhaps we can end this plague that kills more people

than any other bacteria, " he concluded.

N Engl J Med 2001;345:1098-1104.

October 16, 2001

Why does this keep getting sent out?

Infliximab Therapy Associated With Reactivation

Tuberculosis

Infliximab Therapy Associated With Reactivation Tuberculosis

http://orthopedics.medscape.com/reuters/prof/2001/10/10.11/20011010clin0

04.html