Real-world data and Mendelian randomization analysis in assessing adverse reactions of rilonacept.

BACKGROUND

Rilonacept, an interleukin-1 (IL-1) "trap," is FDA-approved for recurrent pericarditis, but research on its adverse reactions is limited due to its recent introduction.

AIM

This study aimed to identify potential adverse reactions associated with rilonacept using the FDA Adverse Event Reporting System (FAERS) and to evaluate long-term effects through Mendelian randomization (MR) analysis.

METHOD

We analyzed all adverse event reports related to rilonacept from the FAERS database between January 2021 and June 2024. Positive signals for adverse reactions were extracted using reporting odds ratios (ROR) and information components (IC). MR analysis was conducted using genetic variants as instrumental variables to explore causal relationships between rilonacept and identified adverse reactions, with sensitivity analyses performed for robustness.

RESULTS

A total of 419 adverse event reports were analyzed, documenting 1847 AEs. Common events included COVID-19, injection site rash, pain, and injection site reaction, categorized into 27 System Organ Classes (SOCs). Notable frequencies were found in Infections and Infestations, Nervous System Disorders, and Skin and Subcutaneous Tissue Disorders. Disproportionality analysis identified positive signals primarily in Skin and Subcutaneous Tissue Disorders, Cardiac Disorders, and Immune System Disorders, with 11 AEs showing positive signals in both Preferred Terms (PTs) and SOCs. MR analysis revealed significant associations between IL-1RN (rilonacept) and allergic urticaria (OR: 1.56), rash (OR: 0.64), and myocarditis (OR: 2.26).

CONCLUSION

Rilonacept is effective for certain inflammatory conditions, but careful monitoring for adverse reactions, particularly involving the immune system, skin, and cardiac issues, is essential.