Increased risk of cardiovascular events under the treatments with Janus kinase inhibitors versus biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a retrospective longitudinal population-based study using the Japanese health insurance database

Objectives To compare the risk of cardiovascular events among Janus kinase inhibitors (JAKIs), biological disease-modifying antirheumatic drugs (bDMARDs) (tumour necrosis factor inhibitors (TNFIs) and non-TNFIs) and methotrexate (MTX) in Japanese patients with rheumatoid arthritis (RA).Methods Using Japanese claims data, patients with RA were enrolled in this study if they had at least one ICD-10 code (M05 or M06), were new users of JAKIs, bDMARDs or MTX between July 2013 and July 2020 and being 18 years old or older. The incidence rate (IR), IR ratio and adjusted hazard ratio (aHR (95% CI)) of cardiovascular events including venous thromboembolism, arterial thrombosis, acute myocardial infarction and stroke were calculated. A time-dependent Cox regression model adjusted for patient characteristics at baseline was used to calculate aHR.Results In 53 448 cases, IRs/1000 patient-years of the overall cardiovascular events were 10.1, 6.8, 5.4, 9.1 and 11.3 under the treatments with JAKIs, bDMARDs, TNFIs, non-TNFIs and MTX, respectively. The adjusted HRs of JAKIs for overall cardiovascular events were 1.7 (1.1 to 2.5) versus TNFIs without MTX and 1.7 (1.1 to 2.7) versus TNFIs with MTX.Conclusions Among patients with RA, individuals using JAKIs had a significantly higher risk of overall cardiovascular events than TNFIs users, which was attributed to the difference in the risk between JAKIs and TNFIs versus MTX. These data should be interpreted with caution because of the limitations associated with the claims database.