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Tuberculin skin test before biologic and targeted therapies: does the same rule apply for all?

  • Observational Research
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Abstract

This study aimed to compare Tuberculin Skin Test (TST) and QuantiFERON®-TB Gold In-Tube (QFT–GIT) test in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients scheduled for biological and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) in a Bacillus Calmette-Guérin-vaccinated population. Adult RA (n = 206) and SpA (n = 392) patients from the TReasure database who had both TST and QFT–GIT prior to initiation of biological and targeted synthetic DMARDs were included in the study. Demographic and disease characteristics along with pre-biologic DMARD and steroid use were recorded. The distribution of TST and performance with respect to QFT–GIT were compared between RA and SpA groups. Pre-biologic conventional DMARD and steroid use was higher in the RA group. TST positivity rates were 44.2% in RA and 69.1% in SpA for a 5 mm cutoff (p < 0.001). Only 8.9% and 15% of the patients with RA and SpA, respectively, tested positive by QFT–GIT. The two tests poorly agreed in both groups at a TST cutoff of 5 mm and increasing the TST cutoff only slightly increased the agreement. Among age, sex, education and smoking status, pre-biologic steroid and conventional DMARD use, disease group, and QFT–GIT positivity, which were associated with a 5 mm or higher TST, only disease group (SpA) and QFT–GIT positivity remained significant in multiple logistic regression. TST positivity was more pronounced in SpA compared to that in RA and this was not explainable by pre-biologic DMARD and steroid use. The agreement of TST with QFT–GIT was poor in both groups. Using a 5 mm TST cutoff for both diseases could result in overestimating LTBI in SpA.

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Availability of data and materials

The data underlying this article were accessed from the TReasure database (URL: https://www.trials-network.org/treasure). The derived data generated in this research will be shared on reasonable request to the corresponding author.

Abbreviations

ACR:

American College of rheumatology

ASAS:

Assessment of spondyloarthritis International Society

BCG:

Bacillus Calmette-Guérin

CDC:

Centers for disease control and prevention

DMARD:

Disease-modifying anti-rheumatic drug

EULAR:

European league against rheumatism

HIV:

Human Immunodeficiency Virus

IFN:

Interferon

IGRA:

Interferon-γ release assay

LTBI:

Latent tuberculosis ınfection

NTM:

Non-tuberculous mycobacteria

QFT–GIT:

QuantiFERON®-TB Gold In-Tube Test

RA:

Rheumatoid arthritis

SpA:

Spondyloarthritis

TNF:

Tumor necrosis factor

TST:

Tuberculin skin test

WHO:

World Health Organization

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Authors and Affiliations

  1. Department of Rheumatology, Trakya University Medical School, 22100, Edirne, Turkey

    Ufuk İlgen & Hakan Emmungil

  2. Rheumatology, Hacettepe University Medical School, Ankara, Turkey

    Ömer Karadağ, Levent Kılıç, İhsan Ertenli, Sedat Kiraz & Umut Kalyoncu

  3. Rheumatology, Ankara Yıldırım Beyazıt University, Ankara, Turkey

    Orhan Küçükşahin & Abdülsamet Erden

  4. Rheumatology, Fırat University Medical School, Elazığ, Turkey

    Süleyman Serdar Koca

  5. Rheumatology, University of Health Sciences, Istanbul, Turkey

    Cemal Bes

  6. Rheumatology, Koç University Medical School, Istanbul, Turkey

    Nilüfer Alpay Kanıtez

  7. Rheumatology, Uludağ University Medical School, Bursa, Turkey

    Ediz Dalkılıç

  8. Rheumatology, İzmir Katip Çelebi University Medical School, İzmir, Turkey

    Servet Akar

  9. Rheumatology, Namık Kemal University Medical School, Tekirdağ, Turkey

    Rıdvan Mercan

  10. Rheumatology, Gülhane Medical School, University of Helath Sciences, Ankara, Turkey

    Muhammet Çınar

  11. Rheumatology, Eskişehir Osmangazi University Medical School, Eskişehir, Turkey

    Timuçin Kaşifoğlu

  12. Rheumatology, Sakarya University Medical School, Adapazari, Sakarya, Turkey

    Emel Gönüllü

  13. Rheumatology, Mustafa Kemal University Medical School, Antakya, Hatay, Turkey

    Gezmiş Kimyon

  14. Rheumatology, Adana City Hospital, Adana, Turkey

    Duygu Ersözlü

  15. Rheumatology, Marmara University Medical School, Istanbul, Turkey

    Pamir Atagündüz

  16. Rheumatology, Akdeniz University Medical School, Antalya, Turkey

    Veli Yazısız

  17. Rheumatology, Ankara University Medical School, Ankara, Turkey

    Aşkın Ateş

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  1. Ufuk İlgen
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Contributions

Conception and design: UI, HE, UK. Data acquisition and analysis: UI, ÖK, HE, SA, LK, UK. Data interpretation: UI, ÖK, HE, OK, SSK, AE, CB, NAK, ED, SA, RM, MC, TK, EG, GK, DE, PA, LK, IE, VY, AA, SK, UK. Drafting and critical review: UI, ÖK, HE, OK, SSK, AE, CB, NAK, ED, SA, RM, MC, TK, EG, GK, DE, PA, LK, IE, VY, AA, SK, UK. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ufuk İlgen.

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Conflict of interest

The authors declare that they have no competing interests.

Ethics approval

Ethical approval was obtained from Hacettepe University Institutional Review Board (KA17/058, May 2017) and Ministry of Health of Turkey (93189304-14.03.01, October 2017).

Consent to participate

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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Supplementary Information

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296_2022_5134_MOESM1_ESM.docx

Supplementary file1 Supplementary Table 1. Comparison of the study groups with entire RA and SpA patients in terms of demographic data, disease-related features, TST and QFT–GIT results, and LTBI treatment rates (DOCX 15 kb)

296_2022_5134_MOESM2_ESM.docx

Supplementary file2 Supplementary Table 2. Performance of TST to predict QFT–GIT for 5, 10, and 15 mm cutoff values (DOCX 12 kb)

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İlgen, U., Karadağ, Ö., Emmungil, H. et al. Tuberculin skin test before biologic and targeted therapies: does the same rule apply for all?. Rheumatol Int 42, 1797–1806 (2022). https://doi.org/10.1007/s00296-022-05134-z

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