Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) confers an increased risk of mortality among patients with RA. However, the optimal treatment strategies remained uncertainty due to limited high-quality evidence.
Research question: In patients with RA-ILD, how does tocilizumab compare to rituximab in terms of prognosis?
Study design and methods: We used the TriNetX US Collaborative Network database to emulate a target trial of RA-ILD patients treated with either tocilizumab or rituximab. Propensity score matching was employed to balance disease severity between groups. Primary and secondary outcomes included all-cause mortality, and medical utilizations risk. Hazard ratios (HRs) were estimated using Cox regression. Subgroup and sensitivity analyses were performed.
Results: Each matched cohort included 1,194 patients. Over 5 years, all-cause mortality did not differ significantly between tocilizumab and rituximab groups (HR: 1.073, 95% CI: 0.881-1.305). Secondary outcomes, including hospitalization and mechanical ventilation, were also comparable. Excluding patients with other Systemic autoimmune rheumatic disease (SARD)-related ILD yielded consistent results. In sensitivity analysis, RA-ILD patients with elevated baseline inflammatory markers experienced higher risks with tocilizumab in mechanical ventilation (HR: 1.936, 95% CI: 1.125-3.331), and all-cause mortality (HR: 1.403 95% CI: 1.013-1.942). Additionally, tumor necrosis factor inhibitors (TNFi)-naïve patients with high inflammatory markers had an increased risk of mechanical ventilation (HR: 1.539, 95% CI: 1.074-2.206).
Interpretation: In this real-world cohort, tocilizumab and rituximab demonstrated comparable effectiveness and safety in RA-ILD. However, among patients with elevated baseline inflammatory markers, rituximab might be a safer choice than tocilizumab.
Keywords: Mortality; interstitial lung disease; medical utilization; rheumatoid arthritis; rituximab; tocilizumab.
Copyright © 2025. Published by Elsevier Inc.