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Do the drug doses of conventional synthetic DMARDs used for the treatment of biologic/targeted-synthetic DMARDs naive rheumatoid arthritis patients affect QuantiFERON-TB Gold Plus test results?

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Abstract

We aimed to obtain the effects of immunosuppressive doses on the QuantiFERON-TB Gold Plus (QFT-Plus) test results in Rheumatoid Arthritis (RA) patients. Besides this, the impact of the TB2 tube in QFT-Plus test was also investigated. This study included RA patients registered to HURBIO and were screened via QFT-Plus test for latent tuberculosis between January 2018 and March 2021, before the initiation of treatment of biologic/targeted-synthetic disease modifying anti-rheumatismal drugs (b/ts-DMARDs). Patients using methotrexate ≥ 10 mg or leflunomide (any dose) or steroids (≥ 7.5 mg prednisolone) at the time of QFT-Plus test were classified as the “high dose” group and the rest of the patients constituted the “low dose” group. The study included 534 RA patients; 353 [66.1%] in the high-dose group and 181 [33.9%] in the low-dose group. While QFT-Plus test was positive in 10.5% (37/353) patients in the high-dose group, it was positive in 20.4% (37/181) patients in the low-dose group (p < 0.001). The percentage of QFT-Plus indeterminate results were similar (around 2%) in both groups. The contribution of the TB2 tube to QFT-Plus test positivity was 6.89%. During a median (inter-quartile range) follow-up period of 23 (7–38) months under treatment of b/ts-DMARDs, latent TB reactivation was not observed. Primer active tuberculosis disease developed in two patients. Positive test results of Interferon-Gamma Release Assays (IGRAs) could decrease as immunosuppressive treatment doses increase in patients with RA and addition of the TB2 tube could increase test sensitivity.

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References

  1. Dinser R, Fousse M, Sester U, Albrecht K, Singh M, Kohler H, Muller-Ladner U, Sester M (2008) Evaluation of latent tuberculosis infection in patients with inflammatory arthropathies before treatment with TNF-alpha blocking drugs using a novel flow-cytometric interferon-gamma release assay. Rheumatology (Oxford) 47(2):212–218. https://doi.org/10.1093/rheumatology/kem351

    Article  CAS  PubMed  Google Scholar 

  2. Lee H, Park HY, Jeon K, Jeong BH, Hwang JW, Lee J, Cha HS, Koh EM, Kang ES, Koh WJ (2015) QuantiFERON-TB Gold In-Tube assay for screening arthritis patients for latent tuberculosis infection before starting anti-tumor necrosis factor treatment. PLoS ONE 10(3):e0119260. https://doi.org/10.1371/journal.pone.0119260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Seyhoglu E, Uyaroglu OA, Erden A, Kilic L, Karadag O, Akdogan A, Bilgen SA, Ertenli I, Kiraz S, Kalyoncu U (2021) QuantiFERON(R)-TB Gold In-Tube test can be used for screening latent tuberculosis before biological treatment in a Bacille Calmette-Guerin (BCG)-vaccinated country: the HUR-BIO single-center real-life results. Clin Rheumatol 40(5):2027–2035. https://doi.org/10.1007/s10067-020-05443-3

    Article  PubMed  Google Scholar 

  4. Carmona L, Gomez-Reino JJ, Rodriguez-Valverde V, Montero D, Pascual-Gomez E, Mola EM, Carreno L, Figueroa M, Group B (2005) Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum 52(6):1766–1772. https://doi.org/10.1002/art.21043

    Article  CAS  PubMed  Google Scholar 

  5. Fragoulis GE, Nikiphorou E, Dey M et al (2022) EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases [published online ahead of print, 2022 Nov 3]. Ann Rheum Dis. https://doi.org/10.1136/ard-2022-223335

    Article  PubMed  Google Scholar 

  6. Farhat M, Greenaway C, Pai M, Menzies D (2006) False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria? Int J Tuberc Lung Dis 10(11):1192–1204

    CAS  PubMed  Google Scholar 

  7. Koydemir HC, Kulah H, Alp A, Uner AH, Hascelik G, Ozgen C (2014) A Fully microfabricated electrochemical sensor and its implementation for detection of methicillin resistance in Staphylococcus aureus. IEEE Sens J 14(6):1844–1851. https://doi.org/10.1109/JSEN.2014.2305152

    Article  CAS  Google Scholar 

  8. Barcellini L, Borroni E, Brown J, Brunetti E, Campisi D, Castellotti PF, Codecasa LR, Cugnata F, Di Serio C, Ferrarese M, Goletti D, Lipman M, Rancoita PM, Russo G, Tadolini M, Vanino E, Cirillo DM (2016) First evaluation of QuantiFERON-TB Gold Plus performance in contact screening. Eur Respir J 48(5):1411–1419. https://doi.org/10.1183/13993003.00510-2016

    Article  CAS  PubMed  Google Scholar 

  9. Allen NP, Swarbrick G, Cansler M, Null M, Salim H, Miyamasu M, Howard J, Boyle J, Lewinsohn D, Lewinsohn D (2018) Characterization of specific CD4 and CD8 T-cell responses in QuantiFERON TB Gold-Plus TB1 and TB2 tubes. Tuberculosis (Edinb) 113:239–241. https://doi.org/10.1016/j.tube.2018.10.014

    Article  CAS  PubMed  Google Scholar 

  10. Nikiphorou E, Buch MH, Hyrich KL (2017) Biologics registers in RA: methodological aspects, current role and future applications. Nat Rev Rheumatol 13(8):503–510. https://doi.org/10.1038/nrrheum.2017.81

    Article  PubMed  Google Scholar 

  11. Hong JY, Park SY, Kim A, Cho SN, Hur YG (2019) Comparison of QFT-Plus and QFT-GIT tests for diagnosis of M. tuberculosis infection in immunocompetent Korean subjects. J Thorac Dis 11(12):5210–5217. https://doi.org/10.21037/jtd.2019.12.11

    Article  PubMed  PubMed Central  Google Scholar 

  12. QIAGEN (2016) QuantiFERON-TB Gold plus (QFT-Plus) ELISA Package Insert Rev. 04.

  13. Brock I, Ruhwald M, Lundgren B, Westh H, Mathiesen LR, Ravn P (2006) Latent tuberculosis in HIV positive, diagnosed by the M. tuberculosis specific interferon-gamma test. Respir Res 7(1):56. https://doi.org/10.1186/1465-9921-7-56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Luetkemeyer AF, Charlebois ED, Flores LL, Bangsberg DR, Deeks SG, Martin JN, Havlir DV (2007) Comparison of an interferon-gamma release assay with tuberculin skin testing in HIV-infected individuals. Am J Respir Crit Care Med 175(7):737–742. https://doi.org/10.1164/rccm.200608-1088OC

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ponce de Leon D, Acevedo-Vasquez E, Alvizuri S, Gutierrez C, Cucho M, Alfaro J, Perich R, Sanchez-Torres A, Pastor C, Sanchez-Schwartz C, Medina M, Gamboa R, Ugarte M (2008) Comparison of an interferon-gamma assay with tuberculin skin testing for detection of tuberculosis (TB) infection in patients with rheumatoid arthritis in a TB-endemic population. J Rheumatol 35(5):776–781

    PubMed  Google Scholar 

  16. Igari H, Ishikawa S, Nakazawa T, Oya Y, Futami H, Tsuyuzaki M, Suzuki K, Matsumura R (2018) Lymphocyte subset analysis in QuantiFERON-TB Gold Plus and T-Spot.TB for latent tuberculosis infection in rheumatoid arthritis. J Infect Chemother 24(2):110–116. https://doi.org/10.1016/j.jiac.2017.09.012

    Article  PubMed  Google Scholar 

  17. Martin J, Walsh C, Gibbs A, McDonnell T, Fearon U, Keane J, Codd MB, Dodd J, Veale D, Fitzgerald O, Bresnihan B (2010) Comparison of interferon gamma release assays and conventional screening tests before tumour necrosis factor alpha blockade in patients with inflammatory arthritis. Ann Rheum Dis 69(1):181–185. https://doi.org/10.1136/ard.2008.101857

    Article  CAS  PubMed  Google Scholar 

  18. Matulis G, Juni P, Villiger PM, Gadola SD (2008) Detection of latent tuberculosis in immunosuppressed patients with autoimmune diseases: performance of a Mycobacterium tuberculosis antigen-specific interferon gamma assay. Ann Rheum Dis 67(1):84–90. https://doi.org/10.1136/ard.2007.070789

    Article  CAS  PubMed  Google Scholar 

  19. Belard E, Semb S, Ruhwald M, Werlinrud AM, Soborg B, Jensen FK, Thomsen H, Brylov A, Hetland ML, Nordgaard-Lassen I, Ravn P (2011) Prednisolone treatment affects the performance of the QuantiFERON gold in-tube test and the tuberculin skin test in patients with autoimmune disorders screened for latent tuberculosis infection. Inflamm Bowel Dis 17(11):2340–2349. https://doi.org/10.1002/ibd.21605

    Article  PubMed  Google Scholar 

  20. Yu DT, Clements PJ, Paulus HE, Peter JB, Levy J, Barnett EV (1974) Human lymphocyte subpopulations. Effect of corticosteroids. J Clin Invest 53(2):565–571. https://doi.org/10.1172/JCI107591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kleinert S, Kurzai O, Elias J, Marten K, Engelke C, Feuchtenberger M, Sandstede J, Frosch M, Tony HP, Kneitz C (2010) Comparison of two interferon-gamma release assays and tuberculin skin test for detecting latent tuberculosis in patients with immune-mediated inflammatory diseases. Ann Rheum Dis 69(4):782–784. https://doi.org/10.1136/ard.2009.113829

    Article  CAS  PubMed  Google Scholar 

  22. Pieterman ED, Liqui Lung FG, Verbon A, Bax HI, Ang CW, Berkhout J, Blaauw G, Brandenburg A, van Burgel ND, Claessen A, van Dijk K, Heron M, Hooghiemstra M, Leussenkamp-Hummelink R, van Lochem E, van Loo IHM, Mulder B, Ott A, Pontesilli O, Reuwer A, Rombouts P, Saegeman V, Scholing M, Vainio S, de Steenwinkel JEM (2018) A multicentre verification study of the QuantiFERON((R))-TB Gold Plus assay. Tuberculosis (Edinb) 108:136–142. https://doi.org/10.1016/j.tube.2017.11.014

    Article  CAS  PubMed  Google Scholar 

  23. Venkatappa TK, Punnoose R, Katz DJ, Higgins MP, Banaei N, Graviss EA, Belknap RW, Ho CS (2019) Comparing QuantiFERON-TB gold plus with other tests to diagnose Mycobacterium tuberculosis infection. J Clin Microbiol. https://doi.org/10.1128/JCM.00985-19

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

No specific funding was received from any bodies in the public, commercial, or not-for-profit sectors to carry out the work described in this article.

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Contributions

Conceived and designed the analysis: ZO, AO, ME, EB, LK, SK, ZS, BŞ, and OK. Collected the data: ZO, AO, ME, EB, LK, SK, ZS, BŞ, and OK. Contributed data or analysis tools: ZO, AO, ME, EB, LK, SK, ZS, BŞ, and OK. Performed the analysis: ZO, AO, ME, EB, LK, SK, ZS, BŞ, and OK. Wrote the paper: ZO, AO, ME, EB, LK, SK, ZS, BŞ, and OK. Other contribution: ZO, AO, ME, EB, LK, SK, ZS, BŞ, and OK.

Corresponding author

Correspondence to Zehra Ozsoy.

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Conflict of Interest

EB received honorary from AbbVie, Novartis, and UCB-Pharma. SK received honorary from AbbVie, Amgen, Johnson, and Johnson, MSD, Novartis, Pfizer, Roche, and UCB-Pharma. OK received honorary from AbbVie, Aristea, Roche, Novartis, Viela-Bio, Zenas Biopharma, Abdi İbrahim, Celltrion, UCB-Pharma, and Menarini. All of the other authors have declared no conflicts of interest.

Ethics approval

Ethical approval was obtained from Hacettepe University Institutional Review Board (GO21/595, 04/05/2021).

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Written informed consent was obtained from each patient regarding the use of clinical data for research purposes. The study was in accordance with the 2013 amendment of the Helsinki declaration.

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Ozsoy, Z., Ozdemir, A., Ekici, M. et al. Do the drug doses of conventional synthetic DMARDs used for the treatment of biologic/targeted-synthetic DMARDs naive rheumatoid arthritis patients affect QuantiFERON-TB Gold Plus test results?. Rheumatol Int 43, 1445–1451 (2023). https://doi.org/10.1007/s00296-023-05320-7

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  • DOI: https://doi.org/10.1007/s00296-023-05320-7

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