Tuberculosis associated with infliximab, a tumor necrosis factor (alpha)-neutralizing agent

Background: Infliximab is a humanized antibody against tumor necrosis facto r (alpha) (TNF-(alpha)) that is used in the treatment of Crohn's disease an d rheumatoid arthritis. Approximately 147,000 patients throughout the world have received infliximab. Excess TNF-(alpha) in association with tuberculo sis may cause weight loss and night sweats, yet in animal models it has a p rotective role in the host response to tuberculosis. There is no direct evi dence of a protective role of TNF-(alpha) in patients with tuberculosis. Methods: We analyzed all reports of tuberculosis after infliximab therapy t hat 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 d isease (17 had disseminated disease, 11 lymph-node disease, 4 peritoneal di sease, 2 pleural disease, and 1 each meningeal, enteric, paravertebral, bon e, genital, and bladder disease). The diagnosis was confirmed by a biopsy i n 33 patients. Of the 70 reports, 64 were from countries with a low inciden ce of tuberculosis. The reported frequency of tuberculosis in association w ith 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 wa s higher than the available background rates. Conclusions: Active tuberculosis may develop soon after the initiation of t reatment with infliximab. Before prescribing the drug, physicians should sc reen patients for latent tuberculosis infection or disease. (N Engl J Med 2 001;345:1098-104.) Copyright (C) 2001 Massachusetts Medical Society.