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

## TL;DR

This study found that treating juvenile arthritis with TNF inhibitors reduces the risk of autoimmune diseases compared to IL-6 inhibitors.

## Contribution

The study provides real-world evidence comparing the risk of autoimmune diseases between two biologic therapies in pediatric arthritis patients.

## Key findings

- TNF inhibitors were associated with a 63% lower risk of autoimmune diseases compared to IL-6 inhibitors.
- Protective effects of TNF inhibitors were consistent across age, sex, and medication subgroups.
- Sensitivity analyses confirmed the robustness of the observed risk differences.

## Abstract

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.

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.

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.

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.