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

N Engl J Med. 2001 Oct 11;345(15):1098-104. doi: 10.1056/NEJMoa011110.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Adverse Drug Reaction Reporting Systems
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / adverse effects*
  • Arthritis, Rheumatoid / drug therapy
  • Crohn Disease / drug therapy
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Infliximab
  • Lung / pathology
  • Male
  • Middle Aged
  • Recurrence
  • Tuberculosis / chemically induced*
  • Tuberculosis / immunology
  • Tuberculosis / pathology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal
  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab