Hepatitis B infection reported with cancer chemotherapy: analyzing the US FDA Adverse Event Reporting System

Abstract

We conducted data mining using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database on spontaneously reported adverse events to evaluate the association between anticancer drug therapy and hepatitis B infection. Reports of hepatitis B infection were retrieved from the FAERS database. The reporting odds ratio (ROR) was used to estimate the association between hepatitis B infection and various anticancer agents and drug combinations. We detected statistically significant risk signals of hepatitis B for 33 of 64 anticancer agents by ROR (26 cytotoxicity drugs and seven molecular‐targeted drugs). We focused on molecular‐targeted drugs and assessed the risk of hepatitis B from specific anticancer drug combinations. The frequency of hepatitis B infection was significantly high for drugs such as rituximab, bortezomib, imatinib, and everolimus. The addition of cyclophosphamide, doxorubicin, and fludarabine to drug combinations additively enhanced the frequency of hepatitis B infection. There were no reports on hepatitis B infection associated with trastuzumab or azacitidine monotherapy. However, trastuzumab‐containing regimens (e.g., combinations with docetaxel or paclitaxel) were correlated with the incidence of hepatitis B infection, similar to azacitidine monotherapy. Our findings suggest that the concomitant use of anticancer drugs, such as trastuzumab, taxane, and azacitidine, may contribute to the risk of hepatitis B infection. The unique signals detected from the public database might provide clues to eliminate the threat of HBV in oncology.

Real-world prevalence of hepatitis B virus reactivation in cancer patients in Taiwan

“…This patient experienced HBV reactivation between consecutive cycles without any prophylaxis and then HBV DNA increased dramatically. Our findings on the higher risk chemotherapy regimens are aligned with the findings from studies published in Taiwan 7,17 and from US FDA data analysis report, 6 but no statistically significant differences were found among all combinations between HBV reactivation and nonreactivation groups.…”

“…6 In addition, rituximab, bortezomib, imatinib, everolimus, transtuzumab, taxane, and azacitidine may contribute to the risk of HBV reactivation. 6 Chen et al. observed that the incidence of HBV reactivation was 10.4 per 100 person–years and similar among various subtypes of hematological malignancy.…”

“…4 Research has shown that systemic chemotherapy agents such as anthracyclines, vinca-alkaloids, methotrexate, cyclophosphamide, and etoposide, are highly associated with HBV reactivation. 5,6 Data from the US FDA adverse event reporting system show that 26 cytotoxicity chemotherapy drugs and 7 molecular-target agents increase the risk of HBV reactivation. 6 In addition, rituximab, bortezomib, imatinib, everolimus, transtuzumab, taxane, and azacitidine may contribute to the risk of HBV reactivation.…”

“…5,6 Data from the US FDA adverse event reporting system show that 26 cytotoxicity chemotherapy drugs and 7 molecular-target agents increase the risk of HBV reactivation. 6 In addition, rituximab, bortezomib, imatinib, everolimus, transtuzumab, taxane, and azacitidine may contribute to the risk of HBV reactivation. 6 Chen et al observed that the incidence of HBV reactivation was 10.4 per 100 person-years and similar among various subtypes of hematological malignancy.…”

Pharmacovigilance evaluation of the relationship between impaired glucose metabolism and BCR‐ABL inhibitor use by using an adverse drug event reporting database

“…These databases are publically available and reflect full adverse event profiles in real clinical settings. Therefore, these databases are used in pharmacovigilance analyses and are useful for evaluating the risk of adverse events reflected in real clinical settings …”