Association of first, second, and third-line bDMARDs and tsDMARD with drug survival among seropositive rheumatoid arthritis patients: Cohort study in A real world setting

Objectives: To determine the association of first, second, and third-line biologic disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib with drug survival among seropositive rheumatoid arthritis (RA) patients. Methods: The study population was composed of 8,018 seropositive RA patients who were prescribed bDMARDs or tofacitinib between January 2014 and January 2019 from the Korean Health Insurance Review and Assessment Service database. First, second, and third-line choice of tumor necrosis factor inhibitors (TNFi) including etanercept, infliximab, adalimumab, and golimumab, as well as non-TNFi including tocilizumab, rituximab, tofacitinib, and abatacept were assessed. Multivariate Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for drug failure according to bDMARD or tofacitinib choice starting from the initial prescription date. Results: Compared to first etanercept users, patients with first tocilizumab (aHR 0.56, 95% CI 0.46–0.68), tofacitinib (aHR 0.27, 95% CI 0.18–0.42), or abatacept (aHR 0.83, 95% CI 0.69–0.99) had lower risk of drug failure. Second choice of tocilizumab (aHR 0.38, 95% CI 0.25–0.55), tofacitinib (aHR 0.23, 95% CI 0.15–0.37), or abatacept (aHR 0.54, 95% CI 0.35–0.84) was associated with lower drug failure risk compared to second etanercept users. Finally, third choice of tocilizumab (aHR 0.32, 95% CI 0.16–0.62) or tofacitinib (aHR 0.35, 95% CI 0.19–0.63) was associated with lower drug failure risk compared to third TNFi users. Conclusion: First and second-line tocilizumab, tofacitinib, or abatacept may lead to improved drug survival. Third-line use of tocilizumab or tofacitinib may be beneficiary in reducing drug failure risk among seropositive RA patients.