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The risk of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) did not significantly increase among dermatology patients who received JAK inhibitors for a median duration of 16 weeks.

A total of 45 randomized clinical trials were ultimately included in the analysis, comprising a total of 12,996 patients receiving JAK inhibitors and 4,925 receiving placebo. The meta-analysis found no significant increase in MACE (RR 0.47, 95% CI 0.28-0.80) or VTE (RR 0.46, 95% CI 0.26-0.80) when comparing the JAK-STAT and placebo arms. There was also no significant difference in serious adverse events (RR 0.92, 95% CI 0.72-1.20) or discontinuations (RR 0.94, 95% CI 0.76-1.19) between the treatment and placebo groups.

The analysis, led by a group of Australian researchers, appears in . The following paper excerpts were edited for length and clarity.

What prompted this investigation?

In 2022, a large, open-label randomized that people with rheumatoid arthritis who received JAK inhibitors may be at higher risk of MACE and VTE, prompting a "" from the FDA, counseling against their use in patients older than 65 years or with preexisting cardiovascular risk factors. Dermatological guidelines have similarly been adapted to recommend against JAK inhibitor use in certain population groups, or only for patients in whom trials of more established therapies including TNF inhibitors have failed.

Previous analyses of these risks have focused on JAK inhibitor use for a single dermatosis or on multiple dermatoses for a single JAK inhibitor. This review evaluated placebo-controlled trials for all JAK inhibitors and all common dermatoses. In evaluating the literature, the investigators' aim was to discern cardiovascular risk and tolerability of these medications in dermatology patients.

What was the key finding?

Most MACEs occurred in people with preexisting cardiovascular risk factors, such as hypertension and diabetes. Short-term risk of MACE or VTE or intolerability was not significantly increased in either the treatment or placebo arm.

What did the analysis uncover regarding the safety and tolerability of JAK inhibitors?

Overall, there were 13 MACEs and 8 VTEs in those receiving JAK inhibitors and 4 MACEs and 1 VTE among people receiving placebo. The pooled IR for MACE and VTE in the treatment and placebo arms was 0.20 and 0.13 per 100 person exposure years, respectively. Neither group's risk ratio reached statistical significance.

The most common treatment-emergent adverse events (AEs) in the analysis were headache, upper respiratory tract infection, and gastrointestinal symptoms such as nausea. There were 428 serious AEs across both cohorts and no significant difference in serious AEs between the two groups.

What are the key takeaways?

According to researchers, the findings should reassure clinicians that prescribing JAK inhibitors in short intervals to patients with low cardiovascular risk profiles appears to be both safe and well tolerated. But given relatively limited evidence, clinicians need to remain judicious in their use of JAK inhibitors when longer durations or higher-risk patient populations are involved.