Assessing the real-world safety of vutrisiran for transthyretin-mediated amyloidosis with polyneuropathy: Based on WHO-VigiAccess and FAERS databases

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: 721 ADR reports in WHO-VigiAccess, 732 in FAERS

• Primary Outcome: Adverse drug reactions associated with vutrisiran treatment

• Nnt Or Sensitivity: Disproportionality signals detected for injection site reactions, systemic reactions, night blindness, and cardiac pacemaker insertion

• Confidence Interval: Not reported

Clinical Application

Findings support enhanced monitoring protocols for known and newly identified adverse events Relevant for TGA post-market surveillance and specialist neurology/cardiology practice; supports PBS safety monitoring requirements Australian patients with ATTR polyneuropathy receiving vutrisiran treatment

Abstract

BACKGROUND: Vutrisiran is a double-stranded siRNA targeting transthyretin mRNA, primarily for the treatment of transthyretin-mediated amyloidosis (ATTR) with polyneuropathy. Understanding its safety in real-world settings is crucial for achieving optimal treatment outcomes for patients. METHODS: This study assessed the safety of vutrisiran for clinical use by analyzing all adverse drug reaction (ADR) reports in WHO-VigiAccess and U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) databases with vutrisiran as the primary suspected drug and by using four disproportionality analysis and Bayesian information component. Weibull distribution was also utilized to predict the time of occurrence of ADR. RESULTS: During the research process, WHO-VigiAccess reported 721 adverse reaction reports related to vutrisiran, while FAERS documented 732 ADR reports. The analysis revealed that: this study not only demonstrated known adverse reactions such as injection site reactions, such as redness, pain, or swelling at the injection site; systemic reactions like fatigue and myalgia; pain in extremity; and potential risks associated with reduced vitamin A levels, but also detected potential safety signals related to drug such as night blindness and cardiac pacemaker insertion. Furthermore, it was observed that in both the WHO-VigiAccess and FAERS databases, the highest reporting rates of ADR were found in the category of general disorders and administration site conditions. It also confirms the importance of monitoring the occurrence of adverse reactions within one year after drug treatment. CONCLUSION: The study identified several known ADRs and detected potential positive signals that may be associated with the drug. These research results provide clinicians with more information to consider and monitor adverse reactions in patients with ATTR-related polyneuropathy after treatment with vutrisiran, offering more evidence for its safety in real-world settings.

References

1. 1.Tong, W., Li, Y., Xu, X., Mao, Y., Zhang, R., Zhao, C., Zhang, J., Du, C., & Feng, J. (2024). Assessing the real-world safety of vutrisiran for transthyretin-mediated amyloidosis with polyneuropathy: Based on WHO-VigiAccess and FAERS databases. PLoS One. https://doi.org/10.1371/journal.pone.0347417