Comparative Effectiveness of Tocilizumab vs Rituximab in Rheumatoid Arthritis-Associated Interstitial Lung Disease

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) confers an increased risk of mortality among patients with RA. However, the optimal treatment strategies remain uncertain due to the limited high-quality evidence available. Research Question: In patients with RA-ILD, how does tocilizumab compare with rituximab in terms of prognosis? Study Design and Methods: This study used the TriNetX US Collaborative Network database to emulate a target trial of patients with RA-ILD treated with either tocilizumab or rituximab. Propensity score matching was used to balance disease severity between groups. Primary and secondary outcomes included all-cause mortality and medical utilizations risk. Hazard ratios (HRs) were estimated by 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 the 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-related interstitial lung diseases yielded consistent results. In sensitivity analysis, patients with RA-ILD 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). In addition, patients naive to tumor necrosis factor inhibitor therapy 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 displayed comparable effectiveness and safety in RA-ILD. However, among patients with elevated baseline inflammatory markers, rituximab might be a safer choice than tocilizumab.