Positive conversion of interferon-γ release assay in patients with rheumatic diseases treated with biologics

  • Hye Won Kim
  • Oh Chan Kwon
  • Sang Hoon Han
  • Min-Chan ParkEmail author


The objective of this study is to investigate whether the type of biologics (TNFi or others) or type of rheumatic diseases (RA or AS) influence the conversion rate of initially negative tuberculosis (TB) screening test results. A total of 119 patients with RA or AS who had negative baseline interferon-γ release assay (IGRA) results assessed by QuantiFERON-TB Gold in tube (QTF-GIT) were included. All patients received biologic agents, and rescreening with QTF-GIT was performed after a median of 25.9 months from the baseline test. Clinical characteristics and IFN-γ levels were compared between converters and non-converters. Logistic regression analysis was performed to identify factors associated with positive conversion. IGRA conversion was found in 14 of 119 patients (11.8%). The converters were older (53.4 ± 14.2 vs 44.4 ± 15.5 years, p = 0.040), had higher baseline TB-specific IFN-γ responses (0.105 [0.018–0.205] vs 0.010 [0.000–0.035] IU/ml, p = 0.001) and higher incidence of active TB (14.3% vs 0.0%, p = 0.013). The number of patients with RA or AS was 9 (64.3%) or 5 (35.7%) in converters, and 45 (42.9%) or 60 (57.1%) in non-converters. In terms of use of biologics, TNFi of monoclonal antibody form was less commonly used in the converters (p = 0.024). In the logistic regression analysis, type of disease and type of biologics used were not associated with IGRA conversion, whereas baseline TB-specific IFN-γ response was significantly associated with IGRA conversion (OR 1.083, 95% CI 1.019–1.151, p = 0.011). Serial monitoring of LTBI with IGRA retesting is needed during biologic treatment, regardless of the type of rheumatic diseases or type biologics used.


Interferon-γ release assay Biologics Tuberculosis Rheumatoid arthritis Ankylosing spondylitis 



This study was supported by a grant of the Korean Health Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI14C1774). We thank Hye Sun Lee, Ph.D. and Sinae Kim, M.S., Biostatistics Collaboration Unit, Yonsei University College of Medicine, for statistical consultation. We also thank Editage ( for English editing.

Author contributions

HWK contributed to data collection and analysis, and manuscript writing. OCK contributed to data collection and analysis, and manuscript writing. HWK and OCK contributed equally as co-first authors in the study. SHH contributed to data collection and analysis, and critically reviewed the manuscript. M-CP contributed to the conception and design of the study, data collection and analysis, manuscript writing, and final approval of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest in relation to this article.

Ethical approval

All procedures were performed in accordance with the ethical standards of the Institutional Review Board of Gangnam Severance Hospital (IRB No: 3-2016-0240) and with the 1964 Helsinki declaration. The approval date of IRB was October 17, 2016.

Related congress abstract publication

Preliminary data of this study was presented in the poster presentation session of EULAR Congress 2017 that was held in Madrid, Spain; Min-Chan Park, Hye Won Kim, Sang Hoon Han (2017) Positive conversion of tuberculosis screening results and incidence of active tuberculosis infection in patients receiving biologic treatment. Ann Rheum Dis 76 Suppl 2:762.; presentation number, FRI0717; and presentation date, June 16, 2017.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of Medicine, The Graduate SchoolYonsei UniversitySeoulSouth Korea
  2. 2.Division of Rheumatology, Department of Internal Medicine, Gangnam Severance HospitalYonsei University College of MedicineSeoulSouth Korea
  3. 3.Division of Infectious Diseases, Department of Internal MedicineYonsei University College of MedicineSeoulSouth Korea
  4. 4.Division of General Internal Medicine, Department of Internal MedicineSeoul National University Bundang HospitalSeongnamSouth Korea

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