Unveiling the tendon toxicity spectrum of anastrozole, letrozole, and exemestane: a real-world pharmacovigilance study.

BACKGROUND

Aromatase inhibitors have been successfully employed in clinical practice for the treatment of breast cancer (BC); however, the accompanying tendon disorders has often been underestimated. This study aimed to conduct a comprehensive empirical investigation and assess tendon disorders associated with third-generation aromatase inhibitors using data from the FDA's FAERS database. The goal was to provide a theoretical foundation for the rational application of these drugs in clinical settings.

METHODS

Reports of tendon disorders related to third-generation aromatase inhibitors were retrieved from the FAERS database, covering the period from the first quarter of 2004 to the first quarter of 2024. The data were further analyzed using proportional analysis and a Bayesian approach to detect signals of tendon disorders induced by the three drugs. Additionally, the clinical characteristics, onset time, correlation, and stratification analysis of tendon disorders associated with the three drugs were examined.

RESULTS

Positive signals for tendon disorders associated with third-generation aromatase inhibitors were identified. At the preferred term (PT) level, twelve positive signals were detected, with trigger finger and tenosynovitis stenosans presenting a significant signal. In terms of onset time, letrozole exhibited the earliest onset at 74 days, whereas exemestane showed the latest onset at 243.5 days. After excluding the effect of combination drugs, a clear association between third-generation aromatase inhibitors and tendon disorders was observed.

CONCLUSION

Analysis of the FAERS database has identified risk trends for tendon disorders associated with third-generation aromatase inhibitors. Furthermore, the study reveals varying degrees of tendon toxicity related to these inhibitors, including distinct time-to-onset profiles and drug-specific signal intensities, providing valuable insights into associated tendon disorders in clinical practice.