The Significance of Sensitive Interferon Gamma Release Assays for Diagnosis of Latent Tuberculosis Infection in Patients Receiving Tumor Necrosis Factor-α Antagonist Therapy

Abstract

ObjectiveWe 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)-α antagonist therapy. This study evaluated the significance of sensitive IGRAs for LTBI screening and monitoring.MethodsBefore starting TNF-α 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-α antagonist therapy.ResultsAt 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 T-SPOT.TB, while QFT-GIT testing showed that 36% (9/25) had conversion during TNF-α 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-α 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.ConclusionThis study demonstrated the need to capitalize on sensitive IGRAs to monitor for LTBI in at-risk patients for a more sensitive diagnosis in countries with an intermediate TB burden.

Comparative Evaluation of QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus in Diagnosis of Latent Tuberculosis Infection in Immunocompromised Patients

“…Thus, the discrepancy between QFT-GIT and QFT-Plus might be affected not only by the differences in the antigenic stimulants (the absence of TB7.7 in the TB1 tube and addition of the TB2 tube) but also by the populations examined and the underlying conditions of the patients as well. However, as observed in previous IGRA studies (9,24,25,32), most of the discordant results (77.8%) were scattered within IFN-␥ levels of 0.30 to 1.00 IU/ml, which cross the assay cutoff ( Fig. 1).…”

“…We reviewed the patients' medical records, including for previous antituberculosis medication, microbiological and radiological studies, and concomitant medication history. At our institution, we made a diagnosis of LTBI primarily by IGRA using QFT-GIT, which is more advantageous than TST in a country with an intermediate M. tuberculosis burden and a mandatory BCG vaccination program (9,28). TST was performed when the IGRA showed indeterminate results according to the discretion of the physician.…”

“…Kourbeti et al reported the importance of M. tuberculosis as an opportunistic infection in patients receiving biologic agents with an odds ratio of 3.73 (95% confidence interval [CI], 1.72 to 8.13; I 2 ϭ 0) (8). Thus, before the initiation of tumor necrosis factor alpha (TNF-␣) inhibitor treatment, screening for LTBI and prophylaxis in patients have become standardized guidelines (9)(10)(11).…”

Elevated Neopterin Levels Are Associated with Increased Tuberculosis Risk in Rheumatoid Arthritis Patients with QuantiFERON Conversion during Biologic Therapy

“…Similar to a recent study showing frequent conversion of LTBI screening tests in RA patients receiving biologic therapy [17,33], 28.9% of our RA patients had QFT-G conversion during one-year biologic therapy using follow-up IFN-γ≧0.35 IU/ml as the criteria. In contrast to the result of no occurrence of TB observed in treated QFT-G converters in one Greek study [17], 7 (13%) of our untreated converters developed active TB.…”

Challenges in screening for latent tuberculosis in inflammatory bowel disease prior to biologic treatment: a UK cohort study

“…However, given that all active cases of TB in our study were considered to be of low epidemiological risk, guidance regarding rescreening strategies might also be needed. For example, in treating patients with IBD who have been screened and who are receiving prolonged and continuing doses of anti-TNF, close liaison with a TB service is advised,20 and even negative IGRA test results should not exclude the possibility of LTBI 6. Any rescreening strategy needs to take into account conversion of TB tests and dynamic IGRA responses during anti TNF-treatment21 and should not exclude patients previously treated with biologics 22.…”