Background/Purpose: Screening for latent tuberculosis infection (LTBI) before the initiation of biologic and targeted synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs) is recommended internationally especially in tuberculosis (TB) endemic areas like Hong Kong. However, there is no gold-standard. The local guideline recommends the use of either tuberculin-skin-test (TST) or interferon-gamma-release-assay (IGRA) before starting b/tsDMARDs for rheumatic diseases. Both tests have reduced sensitivity in immunosuppressed patients and a previous local study has demonstrated that the two tests had fair level of agreement only. We conducted this study to determine whether the dual LTBI screening strategy could reduce the incidence of TB.

Methods: This is a retrospective cohort study. Consecutive patients who have received b/tsDMARDs for rheumatic diseases in a regional hospital in Hong Kong from July 2007 to December 2018 were reviewed. All patients underwent LTBI screening, either with single testing by TST/ IGRA or dual testing by both. They were categorized into single or dual testing group. Background demographics, concurrent medications and choices of biologic were documented. All patients were followed-up regularly since the initiation of biologic agents for at least 6 months. Isoniazid chemoprophylaxis was prescribed if the patient was tested positive for LTBI. The primary outcome of this study was the incidence of TB during the b/tsDMARDs therapy in the single and dual testing groups. The secondary outcomes included the associated factors of TB, the agreement between TST and IGRA, and the safety of the TB chemoprophylaxis.

Results: Two hundred and seventeen patients were included in this study. One hundred and twenty one patients underwent single LTBI testing with either TST (115) or IGRA (6) and 96 patients underwent dual testing. There was no significant difference in the demographic variables between the two groups. The major indication of biologic agents was rheumatoid arthritis (57% in the single test group and 56% in the dual test group). TB occurred in 9 patients in single testing group and one patient in dual testing group (7.43% versus 1.09%, p=0.045 by Fisher’s exact test). Thirty five patients in the single testing group and 36 patients in the dual testing group were tested positive for LTBI and given isoniazid chemoprophylaxis (28.9% versus 45.8%, p=0.007). The agreement between IGRA and TST was 74.5% with the Cohen’s kappa value 0.413. However, in patients on prednisolone at screening, the kappa value was reduced to 0.378 and further to 0.346 in patients on at least 10mg prednisolone daily. Among all the b/tsDMARDs, infliximab use was significantly associated with the incidence of TB (p< 0.001). Reversible hepatotoxicity occurs in 7 out of 71 courses of isoniazid given, which was not significantly different between the two groups.

Conclusion: Dual testing strategy with both TST and IGRA appears to be an effective and safe way to reduce the incidence of TB in patients on biologic agents for rheumatic diseases. It should be considered in TB endemic areas especially in patients who are on prednisolone when undergoing LTBI screening or if infliximab therapy is anticipated.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparison-of-single-and-dual-latent-tuberculosis-screening-strategies-before-the-initiation-of-biologic-and-targeted-therapy-in-rheumatological-patients-in-hong-kong/