Background/Purpose: Janus kinase inhibitors (JAKIs) have shown positive therapeutic impacts on treatments for rheumatoid arthritis (RA), whereas, concerns have been raised about the risk of vascular events such as venous thromboembolism (VTE) based on the results from the clinical trials with a limited number of patients. Thus a population-based study in clinical settings is needed to investigate the safety of JAKIs in the real-world. The purpose of this study was to compare the risk of vascular events among JAKIs users, biological disease-modifying antirheumatic drugs (bDMARDs) (tumor necrosis factor inhibitors [TNFIs] and non-TNFIs) users, and methotrexate (MTX) users in patients with rheumatoid arthritis (RA) using a large health insurance claims data in Japan.

Methods: This retrospective longitudinal population-based study was conducted using claims data provided by Medical Data Vision Co., Ltd (Tokyo, Japan). We defined individuals as new users of JAKIs (tofacitinib, baricitinib, peficitinib, upadacitinib, filgotinib), bDMARDs or MTX if they met all of the following: 1) having at least one ICD10 code (M05 or M06); 2) having at least one prescription of JAKI, bDMARDs, or MTX between July 2013 and July 2020; 3) being over 18 years old; and 4) having prescription of neither JAKIs, bDMARDs nor MTX prior to six months before the index month. The index month was defined as the first month in which cases met all of the above criteria of 1), 2), and 3). Patients were followed from the index month until the last exposure to JAKIs, bDMARDs or MTX, date of loss of follow-up, or the end of follow-up (July 2021), whichever came first. Vascular events included VTE, arterial thrombosis, acute myocardial infarction, and stroke, and were defined when patients had at least one ICD code and medications for each disease. Patients were excluded from the study population if they had a vascular event during six months before the index month. We defined baseline characteristics using the data during the six months prior to the index month, and calculated incidence rate (IR), IR ratio (IRR, JAKIs vs. TNFIs, JAKIs vs. non-TNFI [IL6 inhibitors and abatacept [ABT]]), JAKIs vs. MTX), and adjusted hazard ratio (HR [95% CI]) of the vascular events using a time-dependent Cox regression model after adjusting for age at index month, sex, and comorbidities at baseline.

Results: In this study, 53,448 cases were included. The mean age was 64 years and 73% were female. Median observation period was 32 months. IRs/1,000 patient-years (PY) of the overall vascular events are shown in Table 1. Crude IRR of JAKIs vs. TNFIs was significantly increased, whereas IRRs of JAKIs vs. non-TNFIs as well as JAKIs vs. MTX were not. Adjusted HR of JAKIs for the overall vascular events was 1.7 [1.2–2.3] (vs. TNFIs), 1.4 [1.0–1.9] (vs. non-TNFIs), and 1.2 [0.9–1.6] (vs. MTX), respectively (Figure 1).

Conclusion: JAKIs user had a significantly higher risk of the overall vascular events than TNFIs and non-TNFIs users, and a similar risk to MTX user in patients with RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-of-vascular-events-under-the-treatments-with-janus-kinase-inhibitors-in-patients-with-rheumatoid-arthritis-an-analysis-using-japanese-health-insurance-database/