Target trial emulation of biologic and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis-associated interstitial lung disease.

BACKGROUND

There is limited clinical trial evidence guiding immunosuppressive medication use in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We evaluated the associations between different biologic and targeted synthetic DMARD (b/tsDMARD) treatments with outcomes in RA-ILD patients.

METHODS

We identified RA-ILD patients using Medicare data from 2006 to 2019 and performed emulated target trials using observational data. Propensity score (PS) matched cohorts compared abatacept, janus kinase inhibitors (JAKi), IL-6 inhibitors (IL-6i), and tumor necrosis factor inhibitors (TNFi); each b/tsDMARD was compared in separate two-way comparisons to rituximab initiators using an intention-to-treat framework. The primary outcome was a composite of respiratory hospitalization, lung transplant, or death. We calculated hazard ratios using Cox proportional hazards regression.

RESULTS

We analyzed RA-ILD patients initiating abatacept (n = 694), JAKi (n = 156), IL-6i (n = 389), or TNFi (n = 734), each PS-matched to an equal number of rituximab initiators. There were no statistically significant differences in the risk of the composite outcome of respiratory hospitalization, lung transplant, or death: abatacept (HR 0.87 95%CI 0.75-1.00), JAKi (HR 0.74 95%CI 0.51-1.08), IL-6i (HR 1.08 95%CI 0.88-1.33), and TNFi (HR 1.09 95%CI 0.95-1.25). In secondary analyses, abatacept (HR 0.84 95%CI 0.71-0.98) and JAKi (HR 0.62 95%CI 0.40-0.96) were associated with lower mortality compared to rituximab.

CONCLUSIONS

In target trial emulations, there were no statistically significant differences between rituximab and other b/tsDMARDs for the primary composite outcome. However, abatacept and JAKi were associated with reduced mortality. Randomized controlled trials in RA-ILD are needed to determine optimal treatment.