Association of Abatacept with Lower Mortality Risk Compared to Rituximab in Rheumatoid Arthritis-Associated Interstitial Lung Disease: An Emulated Target Trial.

Abstract

BACKGROUND The optimal treatment strategy for rheumatoid arthritis-associated interstitial lung disease (RA-ILD) remains uncertain, and direct comparative data between biologics is limited. This study aimed to evaluate the effectiveness and safety of abatacept compared with rituximab in patients with RA-ILD. METHODS An emulated target trial was designed using the TriNetX US Collaborative Network database, including patients with RA-ILD, diagnosed between 2007 and 2024. Propensity score matching (PSM) was used to balance baseline characteristics between the two treatment groups (abatacept and rituximab). The primary outcome was all-cause mortality, while secondary outcomes included respiratory events, medical utilization, and infection-related adverse events. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to use Cox proportional hazards models. RESULTS 1,615 patients per group were identified after matching for analysis. Abatacept was associated with a significantly lower risk of all-cause mortality compared with rituximab (HR 0.689, 95% CI 0.581-0.818) and a reduced risk of mechanical ventilation (HR 0.698, 95% CI 0.521-0.934). The subgroup analyses yielded consistent findings. Sensitivity analyses excluding patients with concomitant connective tissue diseases also demonstrated consistent results (mortality, HR 0.679, 95% CI 0.570-0.810), reinforcing the robustness of the findings. CONCLUSION Abatacept was associated with a lower risk of mortality compared with rituximab in patients with RA-ILD. Because clinicians may preferentially reserve abatacept for less aggressive RA-ILD, residual confounding by indication cannot be excluded; thus, the association should not be interpreted as proof of causality. Prospective randomized trials are needed to confirm whether abatacept confers a true survival advantage.