Disproportionality analysis comparing safety profiles of sonidegib and vismodegib based on the FAERS database

This study aims to comprehensively evaluate the long-term safety profiles of hedgehog pathway inhibitors (HPIs), sonidegib and vismodegib, which have been approved for basal cell carcinoma but lack extensive real-world safety data. Using the FDA Adverse Event Reporting System (FAERS) data from 2012 to 2024, we analyzed adverse events (AEs) associated with these drugs. Notably, most reports were from North America and Europe, which may result in limited generalizability to other populations. Four disproportionality analysis algorithms (ROR, PRR, BCPNN, MGPS) were employed to identify significant AEs across 25 System Organ Classes (SOCs). Common AEs included muscle spasms, alopecia, and ageusia. Unexpected AEs, such as triple negative breast cancer (TNBC), squamous cell carcinoma, and complete atrioventricular block for sonidegib, and atrophic glossitis, malignant neoplasms of the eye, and deafness for vismodegib, were also detected. Gender differences in AE signals and median time to onset (TTO) of sonidegib and vismodegib (67 interquartile range [IQR] 23.25-174.50 vs. 56 IQR 18.00-161.00 days) were determined. The findings suggest sonidegib and vismodegib show differences in reporting patterns that may inform clinical hypotheses requiring confirmation in prospective studies. This study provides new safety insights for clinicians, and may improve patient safety. However, as a spontaneous reporting system, FAERS cannot establish causal relationships. These findings should therefore be considered hypothesis-generating and warrant further research.