Tuberculosis Associated with Infliximab, a Tumor Necrosis Factor Neutralizing Agent

Infliximab is a humanized antibody used in the treatment of Crohn's disease and rheumatoid arthritis. It is active against tumor necrosis fact (TNF-a). Infusions of infliximab can be administered in a single dose, a monthly regimen, or on day 0, day 14, day 42, and then every 8 weeks. The half-life of infliximab is 10 days, and its biologic effect persists for up to 2 months.

Infliximab has been given to about 147,000 patients throughout the world since 1998. Through the MedWatch reporting system at the US Food and Drug Administration (FDA), cases of TB after infliximab therapy began to be reported soon after it was introduced in 1998. Between 1998 and 2000 there were 12 reported deaths. For this report, the investigators analyzed all reports of TB related to infliximab that the FDA received as of May 29, 2001.

Infliximab nearly quadruples the incidence of TB. Over a median period of 12 weeks there were 70 reported cases of TB associated with infliximab treatment. In 48 patients, TB developed after three or less treatments. Forty patients had extrapulmonary disease. Of the 17 patients that had disseminated disease, 11 had lymph-node involvement, 4 had peritoneal disease, two had pleural disease and one person each had meningeal, enteric, paravertebral, bone, genital and bladder disease. Diagnosis with TB was confirmed by biopsy in 33 patients.

Within the 70 reported cases, 64 cases were from countries with low rates of TB. The rate of reported cases of TB among patients treated with infliximab was higher than the background rates for their respective countries. The reported frequency of TB with infliximab treatment was much higher than the incidence of other opportunistic infections related to the use of the drug.

The authors did not have complete information about the status of patients with respect to TB infection before they were treated with infliximab. The authors believe that most patients had reactivation disease in view of their age (median, 57 years), the small number with reported exposure to TB, and the low incidence of TB in countries from which reports were received.

The findings of the study have important implications. Infliximab is an effective treatment for two debilitating diseases for which other treatments are often inadequate. According to the study, infliximab may make TB more active due to the drug's immuno-suppressant effect. "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," the researchers said.

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