Abstract
Several case reports of hepatitis B virus reactivation after rituximab administration have been documented. We investigated the association between hepatitis B and C and 15 kinds of molecular-targeted drugs for cancer. We compared two databases, the Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER) of the Pharmaceuticals and Medical Devices Agency (PMDA). Quantitative analysis involved calculating the reporting odds ratio (ROR) and 95％ confidence interval (95% CI) as a measure of disproportionality. ROR is a tool that detects signals of adverse events for individual drugs, with signals detected when the lower limit of the 95% CI of ROR is > 1. We also investigated the timing of the adverse events and the age of the patients. There were 29,017,485 reports in FAERS and 2,079,653 reports in JADER. Signals were detected for rituximab-associated hepatitis B and hepatitis C, trastuzumab-associated hepatitis B, and imatinib-associated hepatitis B. In FAERS, hepatitis B often occurred within 1 month, whereas rituximab-associated hepatitis B often occurred 2-6 months after administration. In JADER, hepatitis B and rituximab-associated hepatitis B often occurred 1-3 months after administration. We conclude that signals of rituximab-associated hepatitis B and hepatitis C, trastuzumab-associated hepatitis B, and imatinib-associated hepatitis B are marked. Analyzing the timing and age of the patient at the occurrence of adverse events may suggest a relationship between drugs and these events.
