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Biphasic emergence of active tuberculosis in rheumatoid arthritis patients receiving TNFα inhibitors: the utility of IFNγ assay
  1. Der-Yuan Chen1,2,3,4,
  2. Gwan-Han Shen5,6,
  3. Yi-Ming Chen1,2,3,
  4. Hsin-Hua Chen1,2,3,
  5. Chia-Wei Hsieh1,2,3,4,
  6. Joung-Liang Lan1,2,3,4
  1. 1National Yang-Ming University, Taipei, Taiwan
  2. 2Institute of Biomedical Science, National Chung-Hsing University, Taipei, Taiwan
  3. 3Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan
  4. 4School of Medicine, Chung-Shan Medical University, Taichung, Taiwan
  5. 5Division of Respiratory and Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
  6. 6Department of Respiratory Therapy, China Medical University, Taichung, Taiwan
  1. Correspondence to Dr J L Lan, Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, No 160, Sec3, Taichung-Kang Road, Taichung 40705, Taiwan; jllan{at}


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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  • Handling editor Johannes WJ Bijlsma

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was obtained from the Clinical Research Ethics Committee of Taichung Veterans General Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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