Comparative Safety of Biologic and Targeted-Synthetic DMARDs in Patients With Rheumatoid Arthritis: A Multi-Database...

To examine the comparative risk of malignancy, venous thromboembolism (VTE), and heart failure (HF) associated with biologic/targeted synthetic disease-modifying antirheumatic drugs (b/ts DMARDs) in patients with rheumatoid arthritis (RA).

We conducted an observational cohort study using 3 US insurance claims databases: Medicare (2009-2019), MarketScan (2009-2020), and Optum's de-identified Clinformatics Data Mart Database (CDM, 2009-2022). We included adults with RA initiating abatacept (reference), tumor necrosis factor inhibitors (TNFi), rituximab, interleukin-6 inhibitors (IL-6i), or Janus kinase inhibitors (JAKi). We used an as-treated approach as the primary analysis to estimate outcome incidence. Inverse probability of treatment weighting was applied to adjust for confounding. Database-specific hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox-proportional hazard models, then combined through random-effects meta-analysis.

We identified 26 908 abatacept, 11 176 IL-6i, 115 437 TNFi, 14 045 JAKi, and 12 097 rituximab initiators. Weighted HR (95% CI) of malignancy was 0.73 (0.60-0.88) for IL-6i, 0.85 (0.60-1.19) for JAKi, 1.30 (1.14-1.49) for rituximab, and 0.93 (0.85-1.02) for TNFi, compared to abatacept. Weighted HR (95% CI) for VTE was 0.92 (0.62-1.35), 1.17 (0.73-1.86), 1.43 (1.50-1.95), and 1.16 (0.93-1.46), respectively. Weighted HR (95% CI) for HF was 1.00 (0.69-1.46), 1.24 (0.62-2.51), 1.52 (1.04-2.22), and 1.54 (1.22-1.94), respectively.

We observed increased risks of malignancy, VTE, and HF among rituximab initiators; an increased risk of HF among TNFi initiators; and a lower risk of malignancy among IL-6i initiators, all compared to abatacept initiators. These findings should be interpreted with caution due to the potential influence of residual confounding.