Risk of major adverse cardiovascular events in patients with rheumatoid arthritis using Janus Kinase inhibitors

초록

Background: The major adverse cardiovascular events (MACE) risk of Janus Kinase inhibitors (JAKi) compared with a tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis has been under scrutiny by regulatory authorities. Objectives: To evaluate safety analysis of the risk of MACE in RA patients receiving JAKi versus those receiving TNFi in a real-world setting. Methods: Using data from the Korean nationwide healthcare claims information database from January 1, 2009, and December 31, 2019, a population-based retrospective cohort study was conducted with patients aged 18 years or older who diagnosed of rheumatoid arthritis, and prescribed any disease-modifying antirheumatic drugs on the same date. We matched each JAKi user to four TNFi user using a propensity score. The primary composite outcome was defined as the first occurrence of MACE, which, was a composite of myocardial infarction, ischemic stroke, and sudden cardiac death. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) calculated by the Cox proportional hazards model was used to compare the risk of MACE in patient receiving JAKi compared with those receiving TNFi. Results: Out of 7049 incident patients with RA, 937 (13.7%) were JAKi users. The crude incidence rates of MACE per 100 person-years were 0.56 (95% CI 0.27–1.18) and 0.85 (95% CI 0.65–1.11) for patients receiving JAKi and TNFi, respectively. HRs showed no significant differences in the risk of MACE between JAKi users and TNFi users, with HRs of 0.70 (95% CI; 0.32–1.54). In a sensitivity analysis of follow up with intent-to-treat approach follow-up, HRs (0.84, 95% CI; 0.45–1.55) was observed. In the subgroup analyzes, there were no significant changes in the risk of MACE irrespective of gender, age, and concomitant of Methotrexate, glucocorticoids, and nonsteroidal anti-inflammatory drugs. Conclusions: Occurrence of MACE in a total of 7049 RA patients initiating treatment with JAKi or TNFi was infrequent (< 1 per 100 person-years). In this study showed a numerically lower but statistically nonsignificant risk of MACE in RA patients receiving JAKi versus those receiving TNFi. The monitoring of potential MACE risk in RA patient is needed elucidate associated risk of MACE in patient receiving JAKi compared with those receiving TNFi.