First-line JAK inhibitors and cardiovascular events: no excess in a Korean cohort

Design

Nationwide claims-based cohort with propensity-matched analysis

Population

6,174 Korean adults with RA starting first-line TNF inhibitor or JAK inhibitor

Primary outcome

Major adverse cardiovascular events

Effect

4.1 vs 3.6 per 1,000 person-years; adjusted HR 0.64 (95% CI 0.28–1.43)

Using Korea's national claims database, this cohort identified 6,174 people newly diagnosed with rheumatoid arthritis between 2010 and 2015 who started a TNF inhibitor (5,152) or a JAK inhibitor (1,022) as their first advanced therapy, and followed them to mid-2024 for myocardial infarction, ischaemic stroke or coronary revascularisation.

Event rates were 4.1 per 1,000 person-years with TNF inhibitors and 3.6 with JAK inhibitors. The adjusted hazard ratio was 0.64 (95% CI 0.28 to 1.43), and 0.72 (0.19 to 2.74) after propensity matching. Subgroups with baseline cardiovascular risk factors showed the same pattern.

This does not overturn the cardiovascular concern raised by the ORAL Surveillance trial, which studied older patients with at least one cardiovascular risk factor and led regulators, including the EMA and FDA, to restrict or warn about JAK inhibitor use in such patients. The Korean cohort was younger and lower risk, events were few, and the intervals are wide enough to include a doubling of risk. Regulatory warnings and guideline positions have not changed.

• Follow current regulatory warnings on JAK inhibitors in patients over 65, smokers and those with cardiovascular risk factors.
• Record cardiovascular risk factors before choosing between a JAK inhibitor and a TNF inhibitor.
• Do not treat this cohort as evidence that JAK inhibitors are safe in high-risk patients.
• Discuss the uncertainty openly with patients for whom a JAK inhibitor is the preferred option.

Why it matters

It adds data from a lower-risk Asian population to a safety question shaped mostly by one trial.

Don't overread it

Intervals are wide and the population was low-risk; this does not show JAK inhibitors are safe in patients with cardiovascular risk factors.

The statistics, in plain English

A hazard ratio of 0.64 with an interval from 0.28 to 1.43 means the data are compatible with JAK inhibitors carrying anywhere from much less to about 40% more risk; after matching, up to nearly three times. With so few events, 'no significant difference' is not the same as 'no difference'.

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