Safety profiles of intravesical Bacillus Calmette-Guerin in bladder cancer

Bladder cancer (BCa) exhibits significant sex disparities, and intravesical Bacillus Calmette-Guerin (BCG) is a widely used treatment for non-muscle invasive bladder cancer (NMIBC). A comprehensive evaluation of intravesical BCG, including the safety profile and adverse events (AEs), is essential. In particular, exploring the sex differences is crucial. We conducted a pharmacovigilance data analysis using real-world big data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. In our study, we analyzed 3,374 cases of intravesical BCG for signal mining. We detected 353 signals at the Preferred Term (PT) level and 10 signals at the System Organ Class (SOC) level when compared to the full FAERS database. When comparing between intravesical BCG and other administration routes, we identified 14 signals at the PT level and 8 signals at the SOC level. Intravesical BCG exhibited lower immune-related AEs (irAEs) risk than anti-PD-1/PD-L1 treatment, but antibiotics increased the risk. Notably, AEs associated with intravesical BCG exhibited significant sex differences. Female patients showed a higher susceptibility to developing allergic diseases such as Reiter’s syndrome and Arthralgia, while male patients were more prone to infectious diseases. Additionally, we highlighted that male patients had higher fatality rates, whereas female patients experienced higher rates of recurrence and irAEs. We have compiled an overview of AEs associated with intravesical BCG. These findings enhance understanding of safety profiles and risks, enabling informed decisions prioritizing patients.

膀胱癌（BCa）存在显著的性别差异，膀胱内注射卡介苗（BCG）是临床广泛用于治疗非肌层浸润性膀胱癌（NMIBC）的手段。全面评估膀胱内BCG的安全性特征与不良事件（AEs）至关重要，其中探索性别差异尤为关键。本研究依托美国食品药品监督管理局不良事件报告系统（FAERS）的真实世界大数据开展药物警戒数据分析，共纳入3374例膀胱内BCG用药病例进行信号挖掘。与FAERS全数据库相比，本研究在首选术语（PT）层面检出353个信号，在系统器官分类（SOC）层面检出10个信号；与其他给药途径的BCG用药相比，又在PT层面检出14个信号、SOC层面检出8个信号。分析显示，膀胱内BCG相关免疫相关不良事件（irAEs）风险低于抗PD-1/PD-L1治疗，但抗生素会升高该风险。值得注意的是，膀胱内BCG相关不良事件存在显著性别差异：女性患者更易罹患赖特综合征、关节痛等过敏性疾病，而男性患者更易发生感染性疾病；此外，男性患者的病死率更高，女性患者的复发率与irAEs发生率则更高。本研究系统梳理了膀胱内BCG相关不良事件的全貌，上述发现加深了对其安全性特征与风险的认知，可为临床个体化诊疗决策提供依据。