N Engl J Med. 2001;345:1098-104.

Tuberculosis associated with infliximab, a tumor necrosis factor

alpha-neutralizing agent.

Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD,

Siegel JN, Braun MM.

Pulmonary Center, Department of Medicine, Boston University School of Medicine,

MA 02118, USA. jkeane@lung.bumc.bu.edu

BACKGROUND: Infliximab is a humanized antibody against tumor necrosis factor

alpha (TNF-alpha) that is used in the treatment of Crohn's disease and

rheumatoid arthritis. Approximately 147,000 patients throughout the world have

received infliximab. Excess TNF-alpha in association with tuberculosis may cause

weight loss and night sweats, yet in animal models it has a protective role in

the host response to tuberculosis. There is no direct evidence of a protective

role of TNF-alpha in patients with tuberculosis. METHODS: We analyzed all

reports of tuberculosis after infliximab therapy that had been received as of

May 29, 2001, through the MedWatch spontaneous reporting system of the Food and

Drug Administration. RESULTS: There were 70 reported cases of tuberculosis after

treatment with infliximab, for a median of 12 weeks. In 48 patients,

tuberculosis developed after three or fewer infusions. Forty of the patients had

extrapulmonary disease (17 had disseminated disease, 11 lymph node disease, 4

peritoneal disease, 2 pleural disease, and 1 each meningeal, enteric,

paravertebral, bone, genital, and bladder disease). The diagnosis was confirmed

by a biopsy in 33 patients. Of the 70 reports, 64 were from countries with a low

incidence of tuberculosis. The reported frequency of tuberculosis in association

with infliximab therapy was much higher than the reported frequency of other

opportunistic infections associated with this drug. In addition, the rate of

reported cases of tuberculosis among patients treated with infliximab was higher

than the available background rates. CONCLUSIONS: Active tuberculosis may

develop soon after the initiation of treatment with infliximab. Before

prescribing the drug, physicians should screen patients for latent tuberculosis

infection or disease.