Complications from Some Anti-Tumor Necrosis Medication s

Mark Borigini, M.D. Health Pro
  • As many patients know by now, tumor necrosis factor plays a key role in causing the inflammation and pain and swelling of joints we see in rheumatoid arthritis. The three anti-tumor necrosis factor medications available currently in the United States are Enbrel, Remicade, and Humira, all of which have been extremely helpful for many patients with rheumatoid arthritis. Unfortunately, these medications have caused, in a small percentage of patients, potentially life-threatening infections, including fungal infections and tuberculosis. Because of this, it is extremely important that the treating rheumatologist screen all patients for tuberculosis before they are started on one of the three “biologic” agents. And if latent infection is discovered (for example, the patient has a positive TB skin test), treatment for preventing active tuberculosis should be started. There is still debate over how to screen for fungal infections.
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    Last year, the United States Centers for Disease Control (CDC) published guidelines regarding preventing tuberculosis infections in patients treated with anti-tumor necrosis factor medications. The physician must take a thorough history from the patient; for example, discussing tuberculosis risk factors such as past or present residence in an area with a high incidence of tuberculosis. Patients then must undergo tuberculosis skin testing; a reaction 5 mm or greater should be interpreted as positive in a patient being considered for Enbrel, Remicade, or Humira.

    The TB skin test, however, might be falsely negative because the patient’s immune system is not functioning correctly due to either the illness or medications being taken which affect the immune system. In addition, a tuberculosis vaccination is used in some countries that can result in a positive TB skin test when patients are tested; therefore immigrants to the United States may have a positive TB skin test, but do not have tuberculosis. Fortunately, new tests for diagnosing latent tuberculosis have been developed. One is a blood test, the Quantiferon test, which has been recommended by the CDC for most populations, but its performance in patients with altered immune systems (including rheumatoid arthritis patients) is not entirely clear.

    Screening for other dangerous infections is not as clear; although there are no CDC guidelines, patients on the tumor necrosis factor inhibiting drugs are at risk for these other infections as well. Histoplasma capsulatum is a fungus found in North and South America, and has been clearly associated with tumor necrosis factor inhibition. Just as tuberculosis can be latent and progress to active disease with immunosuppression, so too can Histoplasma capsulatam. Blood tests can measure levels of antibody to this fungus, or even skin tests may be helpful, but there is such uncertainty regarding their usefulness that routine screening for Histoplasma is not now recommended. The same can be said for Coccidioides immitis, another fungus, found in the southwestern United States and Central and South America. Listeria monocytogenes is a bacteria which can be acquired through eating meat and dairy products; patients on Enbrel, Humira or Remicade might be advised to avoid non-pasteurized dairy products, undercooked meats, and deli foods.

  • Patients and doctors need to be aware of the risk for infection when tumor necrosis factor inhibition is used in the treatment of rheumatoid arthritis. And while this risk is far outweighed by the benefit of these amazing medications, a healthy respect for potential problems does not take a lot of effort, and could avoid complications and interruptions in treatment.
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      Do you have a question about Rheumatoid Arthritis medication or treatment? Send it to Dr. Borigini at or post it on the RA Message Boards.

      Learn more about medications used to treat RA at our Drug Information section.

Published On: November 30, 2006