Short-term JAK inhibitor therapy does not significantly increase serious adverse events

Key takeaways:

• Short-term JAK inhibitor therapy showed no risk increase for MACE (RR = 0.47) or VTE (RR = 0.46).
• It also did not increase serious adverse events (RR = 0.92) or discontinuations (RR = 0.94).

Janus kinase inhibitor therapy in short durations did not significantly increase the risk for major adverse cardiovascular events or venous thromboembolism in patients with low cardiovascular risk profiles, according to a study.

Patrick A. Ireland, MD, of Prince of Wales Hospital and University of New South Wales in Australia, and colleagues further found that treatment with Janus kinase-signal transducer and activator of transcription inhibitors (JAK-STATi) also did not exhibit a significant difference in serious adverse events in these patients vs. those treated with placebo.

“In 2022, a large open-label randomized clinical trial suggested that patients with rheumatoid arthritis receiving JAK-STATi may be at higher risk of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE), prompting a class wide black box warning counselling against their use in patients older than 65 years or with preexisting cardiovascular risk factors,” Ireland and colleagues wrote.

This recommendation also applied to the dermatology community with many populations being advised against taking JAK-STATi therapy, the authors continued. To elucidate the risk for MACE, VTE and other serious adverse events associated with this therapy, Ireland and colleagues conducted a systematic review of 42 randomized clinical trials.

These trials were comprised of 12,996 JAK-STATi therapy-treated patients and 4,925 placebo-treated patients.

The meta-analysis showed that JAK-STATi therapy did not significantly increase the risk for MACE (RR = 0.47; 95% CI, 0.28-0.8) or VTE (RR = 0.46; 95% CI, 0.26-0.8) in the short-term.

Those taking JAK-STATi therapy saw an incidence rate of 0.3 per 100 person-exposure-years, whereas those taking placebo saw an incidence rate of 0.13 per 100 person-exposure-years. The pooled risk ratio for those taking JAK-STATi therapy to those not taking the therapy was 1.13 for MACE (95% CI, 0.35-4.76) and 2.79 for VTE (95% CI, 0.37-123.61). According to the authors, neither risk ratio reached statistical significance.

JAK-STATi therapy was deemed well-tolerated as patients did not experience increased rates of serious adverse events (RR = 0.92; 95% CI, 0.72-1.2) or discontinuations (RR = 0.94; 95% CI, 0.76-1.19) compared with those treated with placebo.

“The results of this review aid to reassure clinicians that the prescribing of these medications in short intervals to patients with low cardiovascular risk profiles appears to be both safe and well tolerated in this cohort,” the authors concluded. “Given the limited evidence, clinicians must remain judicious in their use of these medications for long durations and in high-risk patient populations.”