Cardiovascular risk in patients with rheumatoid arthritis receiving targeted synthetic and biological disease-modifying antirheumatic drugs: a multi-center retrospective cohort study

Abstract

<p><br></p><p><strong>Introduction</strong><br></p><p>Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular events (CVE). Biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may alter the CVE risk in RA through suppression of inflammation. Compared to conventional synthetic DMARDs, tumour necrosis factor inhibitor (TNFi) would decrease the risk of CVE but debatable findings exist for interleukin-6 inhibitors (IL-6i) and JAK inhibitors (JAKi). This study aimed to compare the cardiovascular safety of IL-6i and JAKi to TNFi.</p><p><br></p><p><strong>Methods</strong><br></p><p>We conducted a retrospective cohort study using population-based electronic databases from Hong Kong, Taiwan and Korea. We identified newly diagnosed patients with rheumatoid arthritis who received b/tsDMARDs first time. We followed patients from b/tsDMARDs initiation to the earliest outcome (acute coronary heart disease, stroke, heart failure, venous thromboembolism and systemic embolism) or censoring events (death, transformation of b/tsDMARDs on different targets, discontinuation, and study end). Using TNFi as reference, we applied generalised linear regression for the incidence rate ratio (IRR) estimation adjusted by age, sex, disease duration and comorbidities. Random effects meta-analysis was used for pooled analysis from three sites. </p><p><br></p><p><strong>Results</strong><br></p><p>We identified 8689 participants for this study. Median (interquartile range) follow-up years were 1.45 (2.77) in Hong Kong, 1.72 (2.39) in Taiwan, and 1.45 (2.46) in Korea. Compared to TNFi, the adjusted incidence rate ratios (aIRR) [95% Confidence Interval (CI)] of IL-6i in Hong Kong, Taiwan and Korea are 0.99 (0.25, 3.95); 1.06 (0.57, 1.98); 1.05 (0.59, 1.86) and corresponding aIRR of JAKi are 1.50 (0.42, 5.41); 0.60 (0.26, 1.41); 0.81 (0.38, 1.74), respectively. Pooled aIRRs showed no significant risk of CVE associated with IL-6i [1.05 (0.70, 1.57)] nor JAKi [0.80 (0.48, 1.35)] compared to TNFi.</p><p><br></p><p><strong>Conclusions</strong>​​​​​​​<br></p><p>There was no difference in the risk of CVE among RA patients initiated with IL-6i, or JAKi compared to TNFi. The finding is consistent from Hong Kong, Taiwan and Korea. Cardiovascular safety might not be the major safety concern when selecting these drugs.</p>