Safety of Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis: A Longitudinal Analysis

BACKGROUND: Biologic and targeted synthetic disease-modifying antirheumatic drugs effectively manage rheumatoid arthritis but are associated with varying risks of adverse events. OBJECTIVE: Comparing the risk of key clinical events across biologic and targeted synthetic disease-modifying antirheumatic drugs to guide safer prescribing behavior. METHODS: A population-based cohort study analysed patients with rheumatoid arthritis initiated on one of 12 biologic and targeted synthetic disease-modifying antirheumatic drugs (2009-22) in Hong Kong, with adverse events assessed over 5 years, including major adverse cardiovascular events, infections, malignancies, diabetes mellitus, depression, hospitalisation and all-cause mortality. Marginal structural models with inverse probability weighting addressed time-varying confounding and selection bias. Death was treated as a competing risk, and Bonferroni correction accounted for multiple comparisons. RESULTS: Among 2697 patients with rheumatoid arthritis (4276 treatment episodes), the estimated 5-year cumulative probability of adverse events were broadly comparable across biologic and targeted synthetic disease-modifying antirheumatic drugs: with hospitalisation that ranged from 0.48 (95% confidence interval 0.271, 0.636) for baricitinib to 0.726 (0.665, 0.785) for tocilizumab; mortality from 0.028 (0.002, 0.049) for adalimumab to 0.07 (0.03, 0.118) for abatacept; major adverse cardiovascular events from 0.025 (0.004, 0.046) for golimumab and 0.025 (0.007, 0.046) for adalimumab to 0.072 (0.035, 0.107) for abatacept; infection from 0.213 (0.15, 0.265) for etanercept to 0.389 (0.17, 0.664) for rituximab; malignancy from 0.012 (0, 0.028) for abatacept to 0.116 (0, 0.309) for baricitinib; diabetes from 0.018 (0.003, 0.03) for etanercept to 0.079 (0.015, 0.152) for golimumab; depression from 0 (no events recorded) for baricitinib to 0.029 (0, 0.09) for rituximab; and gastritis from 0.041 (0, 0.078) for baricitinib to 0.114 (0.075, 0.157) for tofacitinib. Risks were compared with etanercept to estimate risk differences, which is the most frequently prescribed agent in Hong Kong with a well-documented safety profile. Tocilizumab was associated with a higher hospitalisation risk (risk difference 0.205; 95% confidence interval 0.104, 0.299) and tofacitinib was associated with a higher gastritis risk (risk difference 0.055; 95% confidence interval 0.001, 0.105). CONCLUSIONS: This study demonstrates broadly similar safety profiles among Biologic and targeted synthetic disease-modifying antirheumatic drugs after rigorous adjustment, alleviating concerns about severe adverse events. These findings provide clinicians with evidence to make informed treatment decisions for patients with rheumatoid arthritis.