From the Guidelines
Tofacitinib and upadacitinib are the JAK inhibitors most strongly associated with Major Adverse Cardiovascular Events (MACE), particularly in patients with cardiovascular risk factors, as evidenced by the ORAL Surveillance study 1. The risk of MACE appears to be dose-dependent, with higher doses of tofacitinib (10 mg twice daily) associated with a greater risk of cardiovascular events, including venous thromboembolism and cancer 1. Key factors that increase the risk of MACE in patients taking JAK inhibitors include:
- Age 65 years and older
- Current or previous long-term smoking
- History of cardiovascular disease (such as heart attack or stroke)
- History of cancer When prescribing JAK inhibitors, clinicians should conduct thorough cardiovascular risk assessments, consider alternative therapies in high-risk patients, and implement regular monitoring of cardiovascular parameters 1. Patients should be educated about recognizing symptoms of cardiovascular events, such as chest pain, shortness of breath, or neurological changes. The use of JAK inhibitors should be cautious in patients at high risk of major adverse cardiovascular events, and alternative therapeutic options should be considered when possible 1.
From the FDA Drug Label
In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers
The JAK inhibitors associated with Major Adverse Cardiovascular Events (MACE) are not explicitly named in the provided drug labels, but it is mentioned that another JAK inhibitor (compared to upadacitinib) has been associated with a higher rate of MACE in RA patients 50 years of age and older with at least one cardiovascular risk factor.
- Key points:
From the Research
JAK Inhibitors Associated with MACE
- Baricitinib: exhibited significant signals for embolic and thrombotic events, ischemic heart disease, and cardiac arrhythmias 3
- Tofacitinib: associated with a signal for hypertension 3, and showed a trend towards an increased risk of MACE, particularly at a dose of 10mg two times per day 4
- Upadacitinib: linked to embolic and thrombotic events 3, and showed a trend towards increased risks of VTE and CVE at a dose of 30mg QD 5
Studies Evaluating MACE Risk
- A pharmacovigilance study using FAERS data found that JAK inhibitors, particularly baricitinib, tofacitinib, and upadacitinib, were associated with increased cardiovascular risk 3
- A retrospective study of patients with rheumatoid arthritis found that tofacitinib, baricitinib, and upadacitinib did not exhibit a high risk for MACE, but were associated with worsening lipid profiles 6
- A post hoc analysis of a phase 3b/4 randomised safety study found that tofacitinib was associated with a higher risk of MACE, particularly at a dose of 10mg two times per day, compared to TNF inhibitors 4
- A systematic review and meta-analysis of patients with atopic dermatitis found that JAK inhibitors may have little-to-no effect on the occurrence of MACE, but the evidence is uncertain 7
- A systematic review and network meta-analysis of patients with inflammatory bowel disease found that JAK inhibitors were not associated with a significantly increased risk of MACE, but some doses of tofacitinib and upadacitinib showed a trend towards increased cardiovascular risk 5