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

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Abstract

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.

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Acknowledgements

We extend our heartfelt thanks to the FDA Adverse Event Reporting System (FAERS) for offering the comprehensive data that was pivotal to this research. Equally appreciated are the efforts of the GWAS databases—deCODE, FINNGEN, and IEU—for their openness in sharing data, which significantly contributed to our understanding of rilonacept’s safety profile.

Funding

No funding was available.

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Author notes

  1. Lihong Liu and Zhenfei Chi these have contributed equally to this work.

Authors and Affiliations

  1. Liaoning University of Traditional Chinese Medicine, The Third Affiliated Hospital of Jinzhou Medical University, Shenyang, China

    Lihong Liu

  2. Shengjing Hospital of China Medical University, Liaoning University of Traditional Chinese Medicine, Shenyang, China

    Zhenfei Chi

  3. Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, No. 79, Chongshandong Road, Huanggu District, Shenyang City, Liaoning Province, China

    Zhe Zhang

Corresponding author

Correspondence to Zhe Zhang.

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Liu, L., Chi, Z. & Zhang, Z. Real-world data and Mendelian randomization analysis in assessing adverse reactions of rilonacept. Int J Clin Pharm (2025). https://doi.org/10.1007/s11096-025-01932-0

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Keywords

  • Adverse reactions
  • FAERS
  • Mendelian randomization analysis
  • Pharmacovigilance
  • Rilonacept

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