Can Skyrizi (Risankizumab) cause cardiotoxicity?

Skyrizi (Risankizumab) and Cardiotoxicity

Based on current evidence, Skyrizi (risankizumab) has been associated with an increased risk of coronary artery disease and atrial fibrillation according to FDA adverse event reporting system analysis. 1

Cardiotoxicity Risk Profile of Skyrizi

Recent pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS) has identified specific cardiovascular concerns with risankizumab:

• Risankizumab was significantly associated with an increased risk of:
  • Coronary artery disease
  • Atrial fibrillation 1

This finding is particularly important as it comes from a comprehensive analysis of over 334,399 adverse events associated with newly approved therapeutic agents for psoriasis, where cardiac adverse events accounted for 3,852 cases.

Mechanism and Context

While the exact mechanism of risankizumab-induced cardiotoxicity is not fully elucidated, it's important to understand the broader context of biologic agent cardiotoxicity:

• Unlike traditional chemotherapeutic agents like anthracyclines that have well-documented dose-dependent cardiotoxicity 2, the cardiotoxicity profile of newer biologics like risankizumab appears to have different mechanisms
• Targeted therapies, while generally considered less toxic than classic chemotherapy drugs, can still cause serious cardiac complications 3
• The European Society of Cardiology (ESC) has recognized that many newer cancer drugs can induce cardiac dysfunction, though specific data on IL-23 inhibitors like risankizumab was not included in their position papers 4

Risk Factors to Consider

When prescribing Skyrizi, consider these risk factors that generally increase susceptibility to drug-induced cardiotoxicity:

• Pre-existing cardiovascular conditions:
  • Heart failure
  • Coronary artery disease
  • Hypertension
  • Arrhythmias 4
• Demographic factors:
  • Advanced age (>65 years)
  • Female sex 4
• Cardiovascular risk factors:
  • Obesity
  • Smoking
  • Diabetes mellitus
  • Hypercholesterolemia 4, 5

Monitoring Recommendations

For patients on Skyrizi who may be at risk for cardiotoxicity:

• Baseline cardiac evaluation before initiating therapy, especially in patients with pre-existing cardiac conditions or risk factors
• Regular monitoring of cardiac function during treatment
• Consider periodic ECG monitoring to detect early signs of arrhythmias, particularly atrial fibrillation
• Be vigilant for symptoms of coronary artery disease, which was the most commonly reported cardiac adverse event with biologics in the FAERS database 1

Clinical Implications

The cardiotoxicity risk with Skyrizi should be weighed against its therapeutic benefits:

• For patients with significant cardiovascular risk factors or pre-existing cardiac disease, consider alternative treatments with potentially lower cardiac risk profiles
• In patients who develop cardiac symptoms while on Skyrizi, prompt evaluation and possible treatment interruption may be necessary
• Collaboration between dermatologists and cardiologists is advisable for high-risk patients requiring Skyrizi treatment

Comparison with Other Biologics

In the FAERS analysis:

• Secukinumab had the highest number of reported cardiac adverse events
• Risankizumab showed significant associations specifically with coronary artery disease and atrial fibrillation
• The overall cardiovascular safety profiles of biological agents used in psoriasis treatment warrant ongoing evaluation 1

This information emphasizes the importance of careful cardiac monitoring throughout treatment with Skyrizi, particularly in patients with pre-existing cardiovascular risk factors.