Screening for tuberculosis infection prior to initiation of anti-TNF therapy

Abstract

T-cell interferon-gamma release assays (IGRAs) are more specific and probably more sensitive than the tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI). Patients with immune-mediated inflammatory diseases (IMID) and suspected LTBI who are candidates for anti-TNF therapy are at a significant risk of TB reactivation yet are prone to false-negative TST results because they are already on immunosuppressive medications. The role of these new blood tests in this patient population is therefore of considerable interest but is currently unclear. The limited published evidence-base shows that agreement between IGRA and TST results is poor in patients with IMID compared to patients without IMID, due to lower proportions of TST-positive results in patients with IMID. Discordant TST-positive, IGRA-negative results are associated with prior BCG vaccination and discordant TST-negative, IGRA-positive results are associated with steroid therapy. Notably, positive IGRA results are more closely associated with the presence of risk factors for LTBI than TST. The percentage of indeterminate IGRAs can be up to 12%. IGRA results in patients already taking anti-TNF agents currently remain uninterpretable. Given the clinical imperative to prevent reactivation of TB in patients starting anti-TNF therapy, screening algorithms should maximise diagnostic sensitivity for detection of LTBI. Therefore, a positive result to either an IGRA or TST, in addition to currently recommended clinical screening for risk factors for LTBI, should prompt consideration of preventive treatment of LTBI in this population.

Fig. 1

Schematic representation of the essential role of TNFα in host immunity against M. tb infection. In patients latently infected with M. tb the risk of incident tuberculosis is 4 to 5 fold higher after initiation of anti-TNF therapy with infliximab. However, it remains unclear whether the TNFα receptor antagonist, etanercept, or the fully humanised monoclonal antibody, adalimumab, increases the risk of TB above the elevated baseline TB incidence rates already documented for patients with IMIDs.