Mao Wei, Jiang Junyan, Xia Yanping, Zhang Lin
Department of Pharmacy, Nanan People's Hospital of Chongqing, Chongqing, China.
Department of Gastroenterology, Nanan People's Hospital of Chongqing, Chongqing, China.
Sci Rep. 2025 Jan 24;15(1):3108. doi: 10.1038/s41598-025-86959-z.
Neuropsychiatric adverse events (AEs) significantly impact the quality of life of patients using avapritinib. However, the majority of current data comes from pre-marketing, with limited real-world studies. Our research aimed to explore post-marketing data of avapritinib. We evaluated the signals of avapritinib-related neuropsychiatric AEs by data mining using the FDA Adverse Event Reporting System (FAERS). Reporting odds ratio (ROR) and information component (IC) were employed to quantify the signals from the first quarter of 2020 through the fourth quarter of 2023. Subsequently, stratified analyses were conducted to further explore the effect of different stratification schemes on the association between avapritinib and neuropsychiatric AEs. Finally, a combination medication analysis was conducted to explore the impact of the co-administration of neuropsychiatric AEs. A total of 2029 neuropsychiatric AEs were reported, and 49 signals were detected, of which 5 were determined to be new signals. Avapritinib was significantly associated with the occurrence of neuropsychiatric AEs (ROR: 1.52, 95% CI: 1.44-1.61; IC: 0.43, IC: 0.35). The stratified analysis found that gender, age and eight preferred terms (PTs), including cerebral haemorrhage, may affect the severity of AEs. Combination medication analysis showed that combining avapritinib with 19 other medications, including prochlorperazine, may increase the risk of neuropsychiatric AEs. The median time-to-onset (TTO) of avapritinib-related neuropsychiatric AEs was 32 (interquartile range [IQR] 2-200) days, with about 65% of cases occurring within the first three months of treatment. An increase in the signal for neuropsychiatric AEs was identified in post-marketing studies of avapritinib. Clinicians are advised to remain vigilant for such events, particularly during the initial stages of treatment with avapritinib.
神经精神不良事件（AEs）对使用阿伐替尼的患者的生活质量有显著影响。然而，目前的大多数数据来自上市前研究，真实世界研究有限。我们的研究旨在探索阿伐替尼的上市后数据。我们使用美国食品药品监督管理局不良事件报告系统（FAERS）通过数据挖掘评估阿伐替尼相关神经精神不良事件的信号。采用报告比值比（ROR）和信息成分（IC）对2020年第一季度至2023年第四季度的信号进行量化。随后，进行分层分析以进一步探讨不同分层方案对阿伐替尼与神经精神不良事件之间关联的影响。最后，进行联合用药分析以探讨神经精神不良事件联合用药的影响。共报告了2029例神经精神不良事件，检测到49个信号，其中5个被确定为新信号。阿伐替尼与神经精神不良事件的发生显著相关（ROR：1.52，95%置信区间：1.44 - 1.61；IC：0.43，IC：0.35）。分层分析发现，性别、年龄以及包括脑出血在内的八个首选术语（PTs）可能会影响不良事件的严重程度。联合用药分析表明，将阿伐替尼与包括丙氯拉嗪在内的其他19种药物联合使用可能会增加神经精神不良事件的风险。阿伐替尼相关神经精神不良事件的中位发病时间（TTO）为32天（四分位间距[IQR]2 - 200天），约65%的病例发生在治疗的前三个月内。在阿伐替尼的上市后研究中发现神经精神不良事件的信号有所增加。建议临床医生对此类事件保持警惕，尤其是在阿伐替尼治疗的初始阶段。
