What are the cardiac effects of Benlysta (belimumab)?

Cardiac Effects of Benlysta (Belimumab)

Benlysta (belimumab) has minimal direct cardiac effects and is not associated with significant cardiotoxicity when used for systemic lupus erythematosus (SLE) treatment. Unlike many immunotherapies and targeted therapies, belimumab has not been linked to specific cardiac adverse events in clinical guidelines or major studies.

Cardiovascular Safety Profile of Belimumab

What We Know About Belimumab

• Belimumab is a human monoclonal antibody that inhibits B-lymphocyte stimulator (BLyS), reducing B-cell differentiation into antibody-producing plasma cells 1
• It is approved for treatment of active, autoantibody-positive SLE in patients with inadequate response to standard therapy 2

Cardiac Effects

• No specific cardiac toxicities are mentioned in SLE treatment guidelines for belimumab 2
• Unlike other immunotherapies such as immune checkpoint inhibitors which can cause myocarditis, pericarditis, arrhythmias, and heart failure, belimumab has not been associated with these cardiac complications 2
• In phase III trials of belimumab, no significant cardiac adverse events were reported as major safety concerns 3

Potential Cardiovascular Benefits

Interestingly, recent research suggests belimumab may actually have positive effects on cardiovascular health in SLE patients:

• A 2025 study found that belimumab treatment improved high-density lipoprotein (HDL) atheroprotective properties in SLE patients 4
• After 6 months of belimumab treatment, patients showed:
  • Increased cholesterol efflux capacity
  • Enhanced antioxidant properties of HDL
  • Increased paraoxonase-1 activity
  • Decreased lipid peroxidation products
  • These improvements may potentially reduce atherosclerosis risk in SLE patients 4

Contrast with Other Immunotherapies

Belimumab's cardiac safety profile appears favorable when compared to other immunotherapies:

• Immune checkpoint inhibitors (ICIs) like ipilimumab, pembrolizumab, and nivolumab have been associated with myocarditis, pericarditis, arrhythmias, cardiomyopathy, and heart failure 2
• The prevalence of ICI-mediated myocarditis is approximately 1.14%, with mortality rates as high as 23% 2
• Tyrosine kinase inhibitors like ibrutinib have been associated with atrial fibrillation (4.5-29% incidence) 2

Monitoring Recommendations

While belimumab does not have specific cardiac monitoring requirements, prudent clinical practice for SLE patients on immunomodulatory therapy includes:

• Baseline cardiovascular risk assessment before initiating therapy
• Regular blood pressure monitoring (SLE patients should maintain BP <130/80 mmHg) 2
• Assessment of lipid levels and cardiovascular risk factors 2
• Consideration of statin therapy based on cardiovascular risk calculation 2

Clinical Implications

1. For patients with pre-existing cardiac conditions:

   • Belimumab appears to be a safer choice compared to other immunotherapies that have documented cardiac toxicities
   • No specific dose adjustments are required for cardiac conditions

2. For patients at high cardiovascular risk:

   • Belimumab may be preferable to other immunomodulators with known cardiac effects
   • The potential improvement in HDL function may provide additional cardiovascular benefit

Key Takeaways

• Belimumab has not been associated with significant direct cardiotoxicity in clinical trials or post-marketing surveillance
• Recent evidence suggests potential cardiovascular benefits through improvement of HDL function
• Standard cardiovascular risk management should be implemented for all SLE patients regardless of specific therapy
• Belimumab represents a safer option from a cardiac perspective compared to many other immunomodulatory therapies

When managing SLE patients with cardiovascular risk factors or pre-existing cardiac disease, belimumab can be considered a relatively cardiac-safe therapeutic option.