Pancreatitis associated with BRAF inhibitors: a disproportionality analysis based on the Food and Drug Administration Adverse Event Reporting System.

Abstract

Background: 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.

Aim: This study aimed to investigate the association between BRAF inhibitors and pancreatitis, and to describe the clinical characteristics of pancreatitis related to these agents.

Method: 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.

Results: 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).

Conclusion: 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.