Randomized prospective crossover study evaluating the performance of Quantiferon TB Gold In-Tube in patients undergoing anti-TNF alpha treatment for screening and monitoring of latent tuberculosis infection

Background: Screening for latent tuberculosis infection (LTBI) is mandatory in patients scheduled for treatment with anti-TNFα agents, due to the increased risk of progression to active disease in subjects previously infected with Mycobacterium tuberculosis (MT). Although there is not a "gold standard" for diagnosis of LTBI, the tuberculin skin test (TST) represents the standardized method worldwide, even if it performs sub-optimally in immunocompromised patients. This observation has led to the development of blood-based assays, including QuantiFERON TB Gold In Tube (QFT-GIT), that appear more specific than TST and may improve the diagnosis of LTBI in patients taking immunosuppressive therapies.Objectives: To investigate the usefulness of QFT-GIT as a tool to identify LTBI in rheumatic patients undergoing treatment with anti-TNFα agents, its agreement with TST, and to evaluate QFT-GIT results 3 months after starting TNFα antagonists.Methods: We conducted a randomized, perspective, crossover study in 111 patients with rheumatic diseases (rheumatoid arthritis n=59; psoriatic arthritis n=36; ankylosing spondylitis n=13; Behçet's syndrome n=3) designated to commence treatment with anti-TNFα agents. Screening for LTBI included QFT-GIT, TST (performed on the same day), chest X-ray and a questionnaire for demographics, history of TB, previous MT contact, BCG vaccination and current immunosuppressive therapy. TST (5U) was evaluated 72 hours later by 2 independent observers. In 61 patients the QFT-GIT was repeated 3 months after starting TNFα antagonists. A blinded interpretation for TST and QFT-GIT results was done. Patients showing screening positive for LTBI received isoniazid prophylaxis before the initiation of TNFα antagonists. All patients signed informed consent before entering the study.Results: Among the 111 patients (70% females; mean age 50 years, range 18-80) enrolled, 80% were taking immunosuppressants at the time of LTBI screening: 88 (79.3%) had a negative, 5 (4.5%) a positive, and 18 (16.2%) an indeterminate QFT-GIT result. Among them, 15 (13.5%) subjects had discrepant results between TST and QFT-GIT (12 patients were TST+/QFT-GIT-, and 3 were TST-/QFT-GIT+). The agreement of the two tests was 86.4% (k=0.26). Among the 61 patients who reached the follow-up at 3 months, 40 remained QFT-GIT negative, 3 converted to positive, and 6 to indeterminate; in particular, 1 patient QFT-GIT positive reverted to negative after isoniazid prophylaxis, whereas among the indeterminate QFT-GIT results, 3 remained indeterminate and 8 reverted to negative.Conclusion: Our study shows a good diagnostic accuracy of QFT-GIT for LTBI in terms of low rate of indeterminate results and a good agreement with TST. The performance of QFT-GIT seems not to be affected by immunosuppressive treatments in our patients, even if a combined use of TST and QFT-GIT is recommended. In addition, the QFT-GIT appears to offer a better chance than TST for monitoring TB infection during anti- TNFα therapy, due to the possible boosting of the skin test result when serial TST is performed.