Trends of adverse events and mortality after DMARDs in patients with rheumatoid arthritis: Interrupted time-series analysis

Objectives: Patients with rheumatoid arthritis (RA) experience adverse events because of the characteristics of the disease and the side effects of medications. We investigated the trends of adverse events and mortality associated with disease-modifying antirheumatic drugs (DMARDs). Methods: We used the Taiwan National Health Insurance Database to enroll patients with incident RA between 2000 and 2017. The 1-year incident rate of gastrointestinal (GI) bleeding and 3-year incident rates of other adverse events and mortality for each calendar-quarter cohort were computed and adjusted using propensity score-based stabilized weights for fair comparisons. Levels and trends of the conventional DMARD era (2000-2002, Phase 1) were compared with those of the TNFi era (2003-2012, Phase 2) and OMA era (2013-2017, Phase 3) by using interrupted time series (ITS) analysis. Results: All patients with RA were prescribed cDMARDs in Phase 1 (2000-2002), and 1%-3% were prescribed either TNFi in phase 2 (2003-2012) or OMAs in phase 3 (2013-2017). The cancer incidence rate was 1.90%, and its mortality rate was 4.19%. After the introduction of TNFi from 2003 to 2012, the main outcomes, except TKA, exhibited a steady or mild decrease in trends. ITS analysis revealed that the slope mildly increased in 2003-2012 compared with that in 2000-2003 by 0.13% for total knee replacement (p = .0322). In 2012-2017 (the OMA era), the events became steady. Conclusion: In patients with RA, the introduction of DMARDs was associated with stable adverse events and mortality rates. Moreover, the introduced new treatment for RA exhibited a good safety profile.