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Biphasic emergence of active tuberculosis in rheumatoid arthritis patients receiving TNFα inhibitors: the utility of IFNγ assay


Objectives The risk of active tuberculosis increases in rheumatoid arthritis (RA) patients receiving antitumour necrosis factor alpha (TNFα) therapy. Longitudinal data concerning serial interferon γ (IFNγ) assays for detecting tuberculosis have been limited. This study investigated the time course of the development of active tuberculosis, and evaluated the utility of serial QuantiFERON-TB Gold (QFT-G) assays for detecting its emergence in RA patients undergoing long-term anti-TNFα therapy.

Methods 242 RA patients who received anti-TNFα therapy and serial QFT-G assays were prospectively evaluated. QFT-G was performed by measuring IFNγ levels in whole blood treated with tuberculosis-specific antigens.

Results Among 242 RA patients, 75 (31.0%) had a positive tuberculin skin test (TST) and 45 (18.6%) had positive QFT-G results, with another nine (3.7%) showing indeterminate QFT-G assay. Isoniazid prophylaxis was given to 37 patients with TST+/QFT-G+ results and 24 TST+/QFT-G− patients with TST induration diameter ≧10 mm. Four patients (three with baseline QFT-G+ results) developed tuberculosis within the first 3 months of anti-TNFα therapy, whereas five patients with baseline TST−/QFT-G− results developed active tuberculosis after 20–24 months' anti-TNFα therapy. Progressively rising levels of released IFNγ (2.17±0.98 vs 5.93±2.92 IU/ml in early secretory antigenic target-6-stimulated well; 1.12±0.84 vs 2.96±1.02 IU/ml in culture filtrate protein-10-stimulated well) were observed in those who developed tuberculosis early in anti-TNFα therapy. QFT-G conversion was found in baseline QFT-G-negative patients who developed tuberculosis late in treatment.

Conclusion The emergence of active tuberculosis follows a biphasic pattern. Persistently high levels of released IFNγ or QFT-G conversion strongly indicate the development of active tuberculosis in patients undergoing long-term anti-TNFα therapy.

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