TNF-blocking agents and tuberculosis: new drugs illuminate an old topic

Abstract

Newer TNF blockers (etanercept, infliximab and adalimumab) have contributed greatly to the control of chronic inflammatory disease. Many of the damaging inflammatory mechanisms that they inhibit are, however, important in maintaining tuberculosis in the latent phase (latent tuberculosis infection or LTBI). There is considerable evidence that links reactivation of LTBI to the use of anti-TNF monoclonal antibody (mAb) treatments, which appear to result in disruption of the granuloma that normally compartmentalizes but does not kill Mycobacterium tuberculosis during LTBI. This effect can be explained, in part, by directly neutralizing TNF, which plays a key role in tuberculosis immunity. To the clinician, dealing with LTBI in patients on these medications is an important issue. Prescribers should seek local expert help in this regard, as global LTBI treatment regimens differ. Nonetheless, screening for and treating LTBI will prevent reactivation in most patients. LTBI screening should include a careful history, tuberculin skin test and chest radiograph. Prophylactic treatment (e.g. isoniazid for 9 months) should be offered to patients with LTBI, in accordance with local advice. False-negative tuberculin skin test results can be expected in these patient groups. False-negative skin tests also mean that clinicians cannot be complacent about patients on TNF blockers who lack evidence of LTBI. On the contrary, because tuberculosis disease can be lethal, all treated patients should be advised to seek medical attention if symptoms suggestive of tuberculosis emerge. The indications for these successful agents are expanding, and efficient management of the LTBI issue should improve their safety profile.