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
Comparative Study
. 2026 Jan 13:16:1744226.
doi: 10.3389/fimmu.2025.1744226. eCollection 2025.

Comparative risk of systemic autoimmune diseases in juvenile idiopathic arthritis treated with TNF-α or IL-6 inhibitors: a real-world cohort study

Jih-Jin Tsai  1   2   3 , Li-Teh Liu  4 , Ping-Chang Lin  1 , Yu-Hsun Wang  5   6 , Yung-Heng Lee #  7   8   9   10 , James Cheng-Chung Wei #  6   11   12   13
Affiliations
Comparative Study

Comparative risk of systemic autoimmune diseases in juvenile idiopathic arthritis treated with TNF-α or IL-6 inhibitors: a real-world cohort study

Jih-Jin Tsai et al. Front Immunol. .

Abstract

Objective: This study aimed to compare the risk of developing systemic autoimmune diseases (SADs) among pediatric patients with juvenile idiopathic arthritis (JIA) treated with tumor necrosis factor inhibitors (TNFi) versus interleukin-6 inhibitors (IL-6i), based on real-world data.

Methods: We conducted a retrospective real-world cohort study using the TriNetX Research Network, which contains data from over 122 million patients. Individuals ≤18 years of age with a diagnosis of JIA who initiated TNFi or IL-6i therapy between January 1, 2013, and December 31, 2024, were included. Propensity score matching (1:1) was performed to balance baseline characteristics. The primary outcome was the incidence of SADs. Hazard ratios (HRs) were estimated using Cox proportional hazards models, and subgroup and sensitivity analyses were conducted to assess robustness.

Results: After matching, 1,192 patients were included in each cohort. The TNFi group demonstrated a significantly lower incidence of SADs than the IL-6i group (17 vs. 45 events; HR = 0.37, 95% CI: 0.20-0.63). Subgroup analyses showed consistent protective effects of TNFi across age, sex, and concomitant medication strata. Sensitivity analyses across three adjusted models confirmed the robustness of the findings, yielding HRs ranging from 0.28 to 0.46.

Conclusion: Among pediatric patients with JIA, TNF inhibitor therapy was associated with a substantially lower risk of developing systemic autoimmune diseases compared with IL-6 inhibitor therapy. These findings may inform biologic selection and long-term safety considerations in pediatric rheumatologic practice.

Keywords: interleukin-6 inhibitors; juvenile idiopathic arthritis; pediatric; systemic autoimmune diseases; tumor necrosis factor inhibitors.

PubMed Disclaimer

Conflict of interest statement

The authors declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author JW declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Flow chart of subject selection of JIA (Juvenile idiopathic arthritis) treated with TNFi versus IL-6i.
Figure 2
Figure 2
Kaplan-Meier plot for risk of systemic autoimmune diseases.
Figure 3
Figure 3
Forest plot of risk of systemic autoimmune diseases exposed to JIA treated with TNFi compared to JIA with IL6i.
See this image and copyright information in PMC

References

    1. Prakken B, Albani S, Martini A. Juvenile idiopathic arthritis. Lancet. (2011) 377:2138–49. doi: 10.1016/S0140-6736(11)60244-4, PMID: - DOI - PubMed
    1. Shiff NJ, Oen K, Kroeker K, Lix LM. Trends in population-based incidence and prevalence of juvenile idiopathic arthritis in manitoba, Canada. Arthritis Care Res (Hoboken). (2019) 71:413–8. doi: 10.1002/acr.23606, PMID: - DOI - PubMed
    1. Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. (2007) 369:767–78. doi: 10.1016/S0140-6736(07)60363-8, PMID: - DOI - PubMed
    1. Tollisen A, Selvaag AM, Aulie HA, Lilleby V, Aasland A, Lerdal A, et al. Physical functioning, pain, and health-related quality of life in adults with juvenile idiopathic arthritis: A longitudinal 30-year followup study. Arthritis Care Res (Hoboken). (2018) 70:741–9. doi: 10.1002/acr.23327, PMID: - DOI - PubMed
    1. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. (2004) 31:390–2., PMID: - PubMed

Publication types

MeSH terms

LinkOut - more resources