第三代芳香化酶抑制剂的肌腱疾病风险：基于FAERS数据库挖掘与分析

Risk of Tendon Disease with Third Generation Aromatase Inhibitors: based on FAERS database mining and analysis

关键词:  第三代芳香化酶抑制剂  FAERS 数据库  肌腱炎  腱鞘炎  肌腱断裂

Key words:  third-generation aromatase inhibitors  FAERS database  tendonitis  tenosynovitis  tendon rupture

摘要:

目的 2023年1月，加拿大卫生部网站警示第三代芳香化酶抑制剂（aromatase inhibitors，AIs）的肌腱疾病风险。然而，第三代AIs相关肌腱疾病的不良事件尚未在真实世界的研究中得到评估和确定。本研究通过对FAERS数据库进行挖掘与分析，探讨两者之间的关系，为临床合理用药提供理论依据。方法 基于2004年1季度至2022年3季度的FAERS数据，采用不成比例分析和贝叶斯分析来检测AIs与肌腱疾病信号，并分析第三代AIs相关肌腱炎、腱鞘炎和肌腱断裂的临床特征、发病时间和关联性。结果 共提取26129份AIs不良事件报告，肌腱疾病报告148份。3种AIs药物均检测到肌腱炎、腱鞘炎和肌腱断裂的阳性信号。阿那曲唑与肌腱炎的统计学相关性最强，阳性信号值最高（ROR 7.72、PRR 7.67、IC 2.93、EBGM 7.64），依西美坦与腱鞘炎的相关性最强（ROR 10.4、PRR 10.35、IC 3.37、EBGM 10.34）。对比阿那曲唑和来曲唑，依西美坦与肌腱断裂可能不相关性（ROR1.41（95%CI＜1）、PRR 1.41（χ2≤4））。阿那曲唑相关的肌腱炎、腱鞘炎和肌腱断裂中位发病时间分别为390天、570天和495天；来曲唑相关肌腱炎和腱鞘炎的中位发病时间分别为30天和45天，肌腱断裂的中位发病为765天；依西美坦的肌腱炎、腱鞘炎中位发病时间分别为360天和150天。结论 本研究通过分析 FAERS 数据确定了第三代AIs导致的肌腱疾病风险趋势，为临床识别AIs诱导的肌腱炎、腱鞘炎和肌腱断裂的不良事件提供了有价值的参考。

Abstract:

OBJECTIVE In January 2023, the Health Canada website warned of the risk of tendon disease with third-generation aromatase inhibitors (AIs). However, adverse events in tendon disease associated with third-generation AIs have not been evaluated and determined in real-world studies. This study explores the relationship between the two by mining and analyzing the FAERS database to provide a theoretical basis for rational clinical use of drugs. METHODS Based on FAERS data from Q1 2004 to Q3 2022, disproportionality analysis and Bayesian analysis were used to detect AIs and tendon disease signals and to analyze the clinical characteristics, onset time, and association of tendinitis, tenosynovitis, and tendon rupture associated with third-generation AIs. RESULTS A total of 26129 adverse event reports of AIs and 148 reports of tendon disease were extracted. Positive signals for tendonitis, tenosynovitis and tendon rupture were detected for all three AIs drugs. Anastrozole had the strongest statistical correlation with tendonitis with the highest positive signal values (ROR 7.72, PRR 7.67, IC 2.93, EBGM 7.64) and exemestane had the strongest correlation with tenosynovitis (ROR 10.4, PRR 10.35, IC 3.37, EBGM 10.34). In contrast to anastrozole and letrozole, exemestane may not correlate with tendon rupture (ROR 1.41 (95% CI < 1), PRR 1.41 (χ2 ≤ 4)). The median onset of anastrozole-associated tendonitis, tenosynovitis, and tendon rupture was 390, 570, and 495 days, respectively; the median onset of letrozole-associated tendonitis and tenosynovitis was 30 and 45 days, respectively, and the median onset of tendon rupture was 765 days; and the median onset of exemestane"s tendonitis and tenosynovitis was 360 and 150 days, respectively. CONCLUSION This study identifies trends in the risk of tendon disease due to third-generation AIs by analyzing FAERS data, providing a valuable clinical reference for identifying adverse events in AIs-induced tendonitis, tenosynovitis, and tendon rupture.