Infliximab is an antibody to tumor necrosis factor (TNF) alpha given to patients with Crohn's disease or rheumatoid arthritis. These patients are at risk for primary or reactivation tuberculosis, often extrapulmonary or miliary. Patients being considered for infliximab therapy should be screened for tuberculosis and given prophylactic or curative antituberculous therapy.
NOTE: Reactivation of other infections is increased in patients with infliximab. Zhang et al (N Engl J Med. 2002; 346: 624) describes reactivation of histoplasmosis in a patient. I would imagine that Mycobacterium avium-intracellulare would also represent a problem.
Before starting infliximab therapy antituberculous prophylaxis is given to all persons with either primary tuberculosis or at high risk for reactivation tuberculosis.
Primary tuberculosis:
(1) conversion to a positive intradermal tuberculin test
(2) greater than 10 mm increase in wheal produced by the test
preferably after contact with a person known to have tuberculosis (but this may be lacking).
Person at risk for reactivation tuberculosis:
(1) history of tuberculosis treated before 1970
(2) history of tuberculosis not treated for at least 6 months, including at least 2 months on rifampin-pyrizinamide combination
(3) in response to an intradermal tuberculin test done more than 10 years after the last BCG vaccination, a wheal larger than 10 mm in diameter or a blister, with no history of active tuberculosis or treatment for tuberculosis
(4) residual tuberculous lesions > 1 cubic cm in size with no certainty that eradicative treatment was received
A person with a history of active tuberculosis treated for at least 6 months including at least 2 months on rifampin-pyrizinamide combination are not considered to be at increased risk for tuberculous reactivation.
where:
• I would think there might be exceptions if rifampin resistant strains were involved.
• False negative intradermal tuberculin tests may occur with immunodeficiency or severe disease.
Chemoprophylaxis regimens:
(1) rifampin and pyrizinamide daily for 2 months (efficacy for prophylaxis only validated in HIV infected persons; regimen not recommended for pregnant women)
(2) rifampin and isoniazid daily for 3 months
(3) isoniazid alone for 9 months in very elderly patients or in patients with hepatic toxicity or cirrhosis
If Mycobacterium tuberculosis is isolated from gastric aspirates or other culture, then the person is switched to a curative regimen.
If active tuberculosis is suspected or diagnosed, then infliximab therapy must be postponed (or discontinued if in progress).
Resuming infliximab therapy in a patient who has developed tuberculosis during therapy is uncertain. Resumption might be considered (with caution) if all of the following are present:
(1) the patient for whom infliximab therapy is considered essential
(2) at least 2 months have passed after completing antituberculous therapy
(3) there is no clinical or radiologic evidence of active tuberculosis
(4) cultures for Mycobacterium tuberculosis are negative
