The significance of sensitive interferon gamma release assays for diagnosis of latent tuberculosis infection in patients receiving tumor necrosis factor-aα antagonist therapy

Objective We compared two interferon gamma release assays (IGRAs), QuantiFERON-TB Gold In- Tube (QFT-GIT) and T-SPOT.TB, for diagnosis of latent tuberculosis infection (LTBI) in patients before and while receiving tumor necrosis factor (TNF)-aα antagonist therapy. This study evaluated the significance of sensitive IGRAs for LTBI screening and monitoring. Methods Before starting TNF-aα antagonist therapy, 156 consecutive patients with rheumatic diseases were screened for LTBI using QFT-GIT and T-SPOT.TB tests. According to our study protocol, QFT-GIT-positive patients received LTBI treatment. Patients positive by any IGRAs were subjected to follow-up IGRA tests after completing LTBI-treatment and/or during TNF-aα antagonist therapy. Results At the initial LTBI screening, 45 (28.9%) and 70 (44.9%) patients were positive by QFT-GIT and T-SPOT.TB, respectively. The agreement rate between IGRA results was 78.8%(k = 0.56; 95% confidence interval [95% CI] = 0.43 to 0.68). Of 29 patients who were positive only by T-SPOT.TB in the initial screening, 83% (19/23) were persistently positive by TSPOT. TB, while QFT-GIT testing showed that 36% (9/25) had conversion during TNF-aα antagonist therapy. By the end of the follow-up period (218 to 1,264 days), four patients (4/137, 2.9%) developed active tuberculosis (TB) diseases during receiving TNF-aα antagonist therapy. Among them, one was Q-T+, one was Q+T-, and the remaining two were Q-T- at the initial screening (Q, QuantiFERON-TB Gold In-Tube; T, T-SPOT.TB; +, positive; -, negative). Two (2/4, 50%) patients with TB reactivation had at least one prior risk factor consistent with previous TB infection. Conclusion This study demonstrated the need to capitalize on sensitive IGRAs to monitor for LTBI in atrisk patients for a more sensitive diagnosis in countries with an intermediate TB burden.