Comprehensive Pharmacovigilance Assessment of Pegvisomant-Associated Adverse Events Using the FDA Adverse Event Reporting System and World Health Organization VigiAccess Databases.

OBJECTIVE

Pegvisomant, a growth hormone receptor antagonist, treats acromegaly in patients inadequately controlled by surgery, radiotherapy, or somatostatin analogs. It lowers insulin-like growth factor-1 levels, with generally favorable tolerability, though rare or delayed adverse events (AEs) may be underrecognized.

METHODS

Adverse event data were obtained from the U.S. FDA Adverse Event Reporting System (FAERS) and from publicly accessible aggregated records retrieved through the World Health Organization VigiAccess interface. Signal detection was performed using four disproportionality algorithms, including reporting odds ratio, proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multi-Item Gamma Poisson Shrinker, as an exploratory pharmacovigilance signal-screening approach rather than a causal comparative analysis. AEs were analyzed at both the system organ class and preferred term levels, and time-to-onset analyses were conducted using FAERS.

RESULTS

A total of 3272 FAERS and 3413 VigiAccess reports were identified. Most frequent AEs involved general disorders, administration-site conditions, and injury-related complications. Significant disproportionality was noted in endocrine-related categories; however, many preferred term-level signals reflected pharmacodynamic or monitoring effects rather than conventional adverse reactions. Clinically relevant suspected AEs were observed in hepatobiliary disorders, injection-site reactions, hypersensitivity, and administration-related issues. Median time to onset in FAERS was 164 days (IQR 1-1052), showing considerable variability and both early and delayed events.

CONCLUSION

This analysis identified reproducible reporting patterns for pegvisomant across 2 pharmacovigilance databases. Endocrine and laboratory-related terms were mainly interpreted as monitoring-related findings, whereas clinically relevant suspected adverse reaction signals were more evident for hepatobiliary events, injection-site reactions, and product administration-related problems. These findings support continued biochemical monitoring, liver surveillance, and careful long-term follow-up during pegvisomant therapy.

PLAIN LANGUAGE SUMMARY: Pegvisomant is a medication used to treat acromegaly by blocking the action of growth hormone. Although it is generally well tolerated, some uncommon or delayed adverse events may not be fully recognized in routine clinical practice. In this study, we analyzed reports from 2 large pharmacovigilance databases, FAERS and VigiAccess, to better characterize the real-world safety profile of pegvisomant. We found that many reported events involved general disorders, administration-site conditions, and treatment-related complications. Some frequently reported endocrine and laboratory-related terms were more likely to reflect treatment monitoring or disease control rather than direct adverse drug reactions. In contrast, more clinically relevant safety signals were mainly related to hepatobiliary disorders, injection-site reactions, and product administration-related problems. We also found that while some events occurred early, others were reported months after treatment initiation, supporting the need for continued follow-up during therapy. These findings provide a broader view of pegvisomant safety and may help clinicians improve long-term monitoring and patient management.