Wang Shoujun, Wang Jinjing, Zhang Huahua, Wang Jiangfeng
Department of Rheumatology and Hematology, Hangzhou Fuyang Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China.
Department of Pharmacy, Hangzhou Fuyang Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China.
Int J Clin Pharm. 2025 Apr 23. doi: 10.1007/s11096-025-01914-2.
The relationship between the development of pancreatitis and the use of BRAF (B-Raf proto-oncogene, serine/threonine kinase) inhibitors remains incompletely understood, primarily due to the infrequency of such cases.
This study aimed to investigate the association between BRAF inhibitors and pancreatitis, and to describe the clinical characteristics of pancreatitis related to these agents.
A disproportionality analysis was conducted using data from the Food and Drug Administration Adverse Event Reporting System between July 2011 and June 2024. The reporting odds ratio (ROR) and information component (IC) were employed to assess the association between BRAF inhibitors and pancreatitis. Additionally, subgroup analysis and time-to-onset analysis were further performed.
A total of 169 cases of pancreatitis were identified in association with BRAF inhibitors: 71 cases with vemurafenib, 63 with dabrafenib, and 35 with encorafenib. The median age of patients was 62 years. Vemurafenib, dabrafenib, and encorafenib all showed a positive signal for pancreatitis, with respective RORs and ICs as follows: vemurafenib (ROR 2.46, 95% CI 1.95-3.10; IC = 1.27, 95% CI 0.88-1.56), dabrafenib (ROR 1.56, 95% CI 1.22-2.00; IC = 0.63, 95% CI 0.21-0.93), and encorafenib (ROR 2.59, 95% CI 1.86-3.62; IC = 1.34, 95% CI 0.77-1.74). The shortest median time-to-onset for pancreatitis was observed with vemurafenib (6.5 days), followed by encorafenib (14.0 days) and dabrafenib (129.5 days).
This study reveals a significant reporting association between BRAF inhibitors and the development of pancreatitis, with a higher risk observed in the early stage of treatment.
胰腺炎的发生与BRAF（B-Raf原癌基因，丝氨酸/苏氨酸激酶）抑制剂的使用之间的关系尚未完全明确，主要原因是此类病例较少见。
本研究旨在调查BRAF抑制剂与胰腺炎之间的关联，并描述与这些药物相关的胰腺炎的临床特征。
利用美国食品药品监督管理局不良事件报告系统2011年7月至2024年6月的数据进行不成比例分析。采用报告比值比（ROR）和信息成分（IC）评估BRAF抑制剂与胰腺炎之间的关联。此外，还进一步进行了亚组分析和发病时间分析。
共确定169例与BRAF抑制剂相关的胰腺炎病例：71例与维莫非尼有关，63例与达拉非尼有关，35例与恩考芬尼有关。患者的中位年龄为62岁。维莫非尼、达拉非尼和恩考芬尼均显示出与胰腺炎相关的阳性信号，各自的ROR和IC如下：维莫非尼（ROR 2.46，95%CI 1.95 - 3.10；IC = 1.27，95%CI 0.88 - 1.56），达拉非尼（ROR 1.56，95%CI 1.22 - 2.00；IC = 0.63，95%CI 0.21 - 0.93），恩考芬尼（ROR 2.59，95%CI 1.86 - 3.62；IC = 1.34，95%CI 0.77 - 1.74）。胰腺炎的最短中位发病时间在维莫非尼组（6.5天），其次是恩考芬尼组（14.0天）和达拉非尼组（129.5天）。
本研究揭示了BRAF抑制剂与胰腺炎发生之间存在显著的报告关联，在治疗早期观察到较高风险。
