From the Guidelines
Rinvoq (upadacitinib) treatment is associated with significant cardiovascular risks, including major adverse cardiovascular events (MACE) and venous thromboembolism (VTE), particularly in patients with pre-existing cardiovascular risk factors, and therefore, its use should be cautiously considered in these patients. The main cardiovascular concerns include increased risk of heart attack, stroke, deep vein thrombosis (DVT), and pulmonary embolism (PE) [ 1 ]. Patients with existing cardiovascular risk factors, including older age, smoking history, hypertension, diabetes, or previous cardiovascular disease, face heightened risk when taking this medication. The European Medicines Agency recommends cautious use of JAK inhibitors, such as upadacitinib, as a first-line agent in patients at risk for adverse cardiovascular outcomes, including age 65 years or older, current or previous long-term smokers, a history of cardiovascular disease, and a history of cancer [ 1 ].
Before starting Rinvoq, patients should undergo cardiovascular risk assessment, and those with significant cardiovascular disease may need to consider alternative treatments. During treatment, patients should be vigilant for warning signs such as chest pain, sudden shortness of breath, leg swelling or pain, and seek immediate medical attention if these occur. Regular monitoring of cardiovascular health is essential throughout the treatment course, and the medication may need to be temporarily discontinued during periods of increased thrombotic risk, such as major surgeries. Key considerations for the use of Rinvoq include:
- Restricted use in advanced therapy-naïve patients, with the FDA label recommending use in patients with prior failure or intolerance to TNF antagonists [ 1 ]
- Cautious use in patients at risk for adverse cardiovascular outcomes, including those with a history of cardiovascular disease or cancer [ 1 ]
- Association with a higher risk of major adverse cardiovascular events and cancer than TNF antagonists in older adults with cardiovascular risk factors [ 1 ]
- Need for careful patient selection, monitoring, and consideration of alternative treatments to minimize cardiovascular risks.
From the FDA Drug Label
Major Adverse Cardiovascular Events Inform patients that RINVOQ/RINVOQ LQ may increase their risk of major adverse cardiovascular events (MACE) including myocardial infarction, stroke, and cardiovascular death Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions (5. 4)].
The cardiovascular risks of Rinvoq (upadacitinib) treatment include:
- Major Adverse Cardiovascular Events (MACE): increased risk of myocardial infarction, stroke, and cardiovascular death
- Patients with a history of smoking or other cardiovascular risk factors are at higher risk Patients should be alert for the development of signs and symptoms of cardiovascular events 2
From the Research
Cardiovascular Risks of Rinvoq (Upadacitinib) Treatment
The cardiovascular risks associated with Rinvoq (upadacitinib) treatment are a concern due to the potential for serious heart-related events.
- Major adverse cardiovascular events (MACE) such as myocardial infarction, stroke, and cardiovascular death have been reported in patients taking upadacitinib 3.
- A post hoc analysis of six phase III trials found that MACE, malignancy, and venous thromboembolism were more frequent in higher-risk cohorts, but the risk was comparable between upadacitinib-treated and adalimumab-treated patients 3.
- Another study found that the incidence rate of MACE was 0.4 patients with events per 100 patient-years in patients with rheumatoid arthritis receiving tofacitinib, another JAK inhibitor 4.
- Upadacitinib has been associated with an increased risk of serious infections, herpes zoster, and non-melanoma skin cancer, but the risk of MACE was generally similar across treatment groups 3, 5, 6.
Risk Factors for Cardiovascular Events
Several risk factors have been identified for cardiovascular events in patients taking upadacitinib, including:
- Age ≥50 years 3
- Presence of ≥1 cardiovascular risk factor 3
- Traditional cardiovascular risk factors such as hypertension and high total cholesterol to high-density lipoprotein (HDL) cholesterol ratio 4
- Increased erythrocyte sedimentation rates 4
Safety Profile of Upadacitinib
The safety profile of upadacitinib has been evaluated in several studies, including a pooled analysis of six phase III trials and a long-term safety analysis of over 15,000 patient-years of exposure.
- The most common adverse events reported with upadacitinib were herpes zoster, non-melanoma skin cancer, and elevations in creatine phosphokinase levels 6.
- Serious adverse events, including deaths, serious infections, major adverse cardiovascular events, and malignancies, were observed, but the rates were generally low 3, 5, 6.