Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2022 Jun 27;24(1):157.
doi: 10.1186/s13075-022-02842-6.

Comparison of developing tuberculosis following tumor necrosis factor inhibition and interleukin-6 inhibition in patients with rheumatoid arthritis: a nationwide observational study in South Korea, 2013-2018

Seung Min Jung  1 , Minkyung Han  2 , Eun Hwa Kim  2 , Inkyung Jung #  3 , Yong-Beom Park #  4
Affiliations
Observational Study

Comparison of developing tuberculosis following tumor necrosis factor inhibition and interleukin-6 inhibition in patients with rheumatoid arthritis: a nationwide observational study in South Korea, 2013-2018

Seung Min Jung et al. Arthritis Res Ther. .

Abstract

Background: Tumor necrosis factor (TNF) inhibitors increase the risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA). This study compared the incidence of TB after treatment with TNF inhibitors and tocilizumab in patients with RA, separately in those who were treated for latent tuberculosis infection (LTBI) and those without evidence of LTBI.

Methods: This study included patients with RA who initiated TNF inhibitors and tocilizumab between December 2013 and August 2018. Patient data were collected from the nationwide database of the Health Insurance Review and Assessment service in South Korea. The incidence of TB was compared among different biologic drugs in patients with or without LTBI treatment.

Results: Of 4736 patients, 1168 were treated for LTBI and 48 developed TB (554.9 per 100,000 person-years). When compared based on etanercept, infliximab showed a higher risk of TB (adjusted incidence rate ratio 2.71, 95% confidence interval 1.05-7.01), especially in patients without evidence of LTBI. Other TNF inhibitors and tocilizumab showed a comparable incidence of TB, regardless of treatment for LTBI. There was no significant difference in TB incidence after biologic therapy between patients with and without LTBI treatment (627.9/100,000 vs. 529.5/100,000 person-years). In patients treated for LTBI, no differential risk of TB was observed among biologic drugs.

Conclusions: The incidence of TB was not significantly different among biologic drugs in the current era, except for infliximab in patients who were not treated for LTBI. Treatment of LTBI might alleviate the drug-specific risk of TB in patients with RA.

Keywords: Biologic therapy; Latent tuberculosis; Rheumatoid arthritis; TNF inhibitors; Tocilizumab; Tuberculosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of patient selection. Patients with rheumatoid arthritis (RA) who started tumor necrosis factor (TNF) inhibitors or tocilizumab between December 2013 and April 2018 were selected from a nationwide database maintained by the Health Insurance Review and Assessment service. According to the exclusion criteria, 6099 patients were selected for the analysis (the incidence of tuberculosis [TB] in these patients including switchers are presented in the Supplement). To avoid the unclear association between biologic agents and TB in patients who switched biologic drugs, we analyzed the incidence of TB in patients who were treated with only one type of TNF inhibitor or tocilizumab during the follow-up. Further, patients who developed TB at > 3 months after stopping the biologic drug were excluded from the analysis because TB was considered to be irrelevant to biologic therapy in these patients. A total of 4736 patients with RA were included for the final analysis RA, rheumatoid arthritis; TNF, tumor necrosis factor; TB, tuberculosis; LTBI, latent tuberculosis infection
Fig. 2
Fig. 2
Cumulative incidence of tuberculosis (TB) in patients with rheumatoid arthritis (RA) who received biologic therapy. The cumulative incidence rate of TB was evaluated using the Kaplan–Meier method, and the differences among biologic therapies were compared using the log-rank test with multiple comparison adjustment. Infliximab showed a significantly higher risk of TB than etanercept (P = 0.04). The table shows the incidence rate of TB in patients with RA stratified by follow-up duration (< 0.5, 0.5–1, 1–3, and ≥ 3 years) CI, confidence interval
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Smolen JS, Steiner G. Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov. 2003;2:473–488. doi: 10.1038/nrd1109. - DOI - PubMed
    1. Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, et al. Rheumatoid arthritis Nat Rev Dis Primers. 2018;4:18001. doi: 10.1038/nrdp.2018.1. - DOI - PubMed
    1. Singh JA, Cameron C, Noorbaloochi S, Cullis T, Tucker M, Christensen R, et al. Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis. Lancet. 2015;386:258–265. doi: 10.1016/S0140-6736(14)61704-9. - DOI - PMC - PubMed
    1. Ramiro S, Sepriano A, Chatzidionysiou K, Nam JL, Smolen JS, van der Heijde D, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2017;76:1101–1136. doi: 10.1136/annrheumdis-2016-210708. - DOI - PubMed
    1. Carmona L, Hernandez-Garcia C, Vadillo C, Pato E, Balsa A, Gonzalez-Alvaro I, et al. Increased risk of tuberculosis in patients with rheumatoid arthritis. J Rheumatol. 2003;30:1436–1439. - PubMed

Publication types

MeSH terms

-