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


CONCLUSIONS
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.
National Yang-Ming University, Taipei, Taiwan.
Der-Yuan
DY
Chen
Gwan-Han
GH
Shen
Yi-Ming
YM
Chen
Hsin-Hua
HH
Chen
Chia-Wei
CW
Hsieh
Joung-Liang
JL
Lan
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D000068800:Etanercept; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D007371:Interferon-gamma / Q000032:analysis* / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000175:diagnosis* / Q000276:immunology; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000068879:Adalimumab; D000068800:Etanercept