Investigating bleeding adverse events associated with BTK inhibitors in the food and drug administration adverse event reporting system (FAERS)

This study analyzed the bleeding adverse events (AEs) resulting from the treatment of B-cell lymphoma with Bruton tyrosine kinase (BTK) inhibitors, according to reports in the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) Bleeding AEs associated with BTK inhibitors (including ibrutinib, zanubrutinib, and acalabrutinib) from the first quarter of 2013 to the third quarter of 2023 were extracted. Reporting odds ratio (ROR) and proportional reporting ratio (PRR) were reported. Preferred Terms (PTs) of Medical Dictionary for Regulatory Activities (MedDRA) terms were mapped to System Organ Class terms (SOC) terms and analyzed bleeding AEs associated with three BTK inhibitors. A total of 463 cases of bleeding AEs were included. Contusion, subcutaneous hemorrhage, hematuria, and cerebral hemorrhage were included in PTs. Blood urine was present and subdural hematoma were also reported. The incidence of bleeding AEs was higher with ibrutinib (Case number = 10,696) than with zanubrutinib (Case number = 213) and acalabrutinib (Case number = 314). Our findings indicate that bleeding AEs linked to BTK inhibitors in various conditions underscore the need for cautious clinical decision-making, particularly in nervous system disorders, injuries, poisoning, surgical complications, vascular disorders, and others.

本研究基于美国食品药品监督管理局（Food and Drug Administration, FDA）不良事件报告系统（FAERS）的公开报告数据，分析了布鲁顿酪氨酸激酶（Bruton tyrosine kinase, BTK）抑制剂治疗B细胞淋巴瘤所引发的出血类不良事件（AEs）。研究提取了2013年第一季度至2023年第三季度期间，与BTK抑制剂（包括依鲁替尼（ibrutinib）、泽布替尼（zanubrutinib）及阿卡替尼（acalabrutinib））相关的出血不良事件报告。本研究采用报告比值比（ROR）与比例报告比值比（PRR）开展数据分析，并将医疗监管活动词典（Medical Dictionary for Regulatory Activities, MedDRA）的首选术语（PTs）映射至系统器官分类（System Organ Class, SOC）术语，进而对三种BTK抑制剂相关的出血不良事件进行分析。本研究共纳入463例出血不良事件病例，其首选术语涵盖挫伤、皮下出血、血尿与脑出血；同时亦有尿血及硬膜下血肿的相关报告。依鲁替尼（病例数=10696）的出血不良事件发生率高于泽布替尼（病例数=213）与阿卡替尼（病例数=314）。本研究结果表明，各类临床场景下与BTK抑制剂相关的出血不良事件，提示临床需谨慎制定决策，尤其在神经系统疾病、损伤、中毒、手术并发症及血管疾病等领域。