Evaluation Of The Usefulness Of Interferon-Gamma Release Assays and Tuberculin Skin Test For Detection Of Latent Mycobacterium Tuberculosis Infection In Korean Rheumatic Patients With Biologic Agents

Abstract

Background/Purpose: The screening for and treatment of latent tuberculosis infection (LTBI) before starting biologic agents is crucial to prevent reactivation and resultant serious infection. Several national guidelines recommended to test tuberculin skin test (TST) initially and Interferon-γ Release Assay (IGRA) if TST result is indeterminate. In Korea with an intermediate tuberculosis(TB) burden, national guideline recommends use of both IGRA and TST for detection of LTBI before starting biologic therapies, and chemopreventive TB treatments are recommend in case of positive IGRA or TST results. Our study was conducted to estimate the concordance between QuantiFERON-TB Gold in tube Test (QFT-GIT) as an IGRA and TST, and to evaluate the difference in the occurrence of active TB in patients who are candidates of biologic agents who receive both QFT-GIT and TST compared with those who receive either TST or QFT-GIT alone for detection of LTBI.

Methods: A total of 959 patients who received both QFT-GIT and TST from Jan. 2004 to Dec. 2012 at Hanyang University Hospital for Rheumatic Diseases were recruited for the concordance between the 2 tests. The concordance between the 2 tests was estimated by Cohen’s kappa (κ). A total of 842 patients who performed QFT-GIT or TST and used biologics from Jan. 2007 to Dec. 2012 were recruited for the usefulness of LTBI screening test. The screening test of LTBI, TB prophylaxis, TB occurrence, and clinical characteristics were examined. Among 842 patients, 260 patients received only TST, 149 patients received only QFT-GIT, and 436 patients received both QFT-GIT and TST. The occurrence of TB according to the screening method of LTBI was identified. The incidence rates of active TB were calculated as number of events per 100,000 person-years exposure.

Results: The concordance between QFT-GIT and TST was low in the whole group (κ = 0.312). A total of 5 patients developed TB after initiation of biologics according to the screening guideline of LTBI. Among them, extra-pulmonary TB occurred in 3 patients. Some patients did not comply with LTBI prophylactic strategy. TB occurred in 2 patients according to LTBI prophylactic strategy (Table). TB incidence in the group that received both QFT-GIT and TST was 151.05/100,000 person-years and that in the group that received only TST was 169.78/100,000 person-years among the patients who complied with LTBI prophylactic strategy.

Conclusion: The concordance between QFT-GIT and TST was low. TB did not occur in patients who received TB prophylaxis after positive results by either only TST strategy or QFT-GIT & TST strategy. TB incidence in patients who performed both QFT-GIT and TST and prophylaxis seems to be lower than that in those who performed only TST and prophylaxis. However, it was difficult to calculate the significant of this difference or superiority because the observation period was short.