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

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.