Potential benefits of biologics on stroke and mortality in patients with rheumatoid arthritis: A nationwide population-based cohort study in Taiwan

Aim: To examine the changes in the risks of death and cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients treated with conventional synthetic or biologic disease-modifying antirheumatic drugs (csDMARD or bDMARD) during 1997-2013. Methods: Two cohorts of RA patients and their matched controls were identified from the National Health Insurance Research database. There were 1569 patients in the csDMARD cohort who received cyclosporine ≥50 mg/d with concomitant usage of ≥2 csDMARDs during 1997-2003. There were 1530 patients in the bDMARD cohort if patients had ≥1 claim for bDMARD during 2003-2011. Adjusted hazard ratios (aHRs) for the risk of death, myocardial infarction, and stroke, were assessed using the Kaplan-Meier survival curves and the Cox proportional hazards models. Results: Compared with matched cohorts, the incidence of death was higher with csDMARD with a more than 6-fold increase (csDMARD vs controls: 33% vs 5%); while it only increased with a much smaller magnitude with bDMARD (bDMARD vs controls: 15% vs 11%). In addition, an increase in the reduction of incidence rate of stroke with bDMARD (bDMARD vs controls: 2% vs 5%) than that with csDMARD (csDMARD vs controls: 3% vs 4%) was found. Results from multivariate analysis showed that RA patients receiving bDMARD had a significantly lower increase in the risk of deaths (aHR 1.05; 95% CI 0.84-1.33) compared with those receiving csDMARD (aHR 8.75; 95% CI 7.43-10.31). In addition, bDMARD was associated with a higher reduction in the risk of stroke compared with csDMARD (bDMARD: aHR 0.37; 95% CI 0.22-0.62; csDMARD: aHR 0.73; 95% CI 0.51-1.05). Conclusion: Biologics used in RA patients have been shown to have a beneficial impact on improving clinical outcomes, including decreased risks of death and stroke. The economic burden from costs of biologics may be alleviated by improving outcomes.