Abstract
Breakpoint cluster region‐Abelson murine leukemia (BCR‐ABL) inhibitors markedly improve the prognosis of chronic myeloid leukemia. However, high treatment adherence is necessary for successful treatment with BCR‐ABL inhibitors. Therefore, an adequate understanding of the adverse event profiles of BCR‐ABL inhibitors is essential. Although many adverse events are observed in trials, an accurate identification of adverse events based only on clinical trial results is difficult because of strict entry criteria or limited follow‐up durations. In particular, BCR‐ABL inhibitor‐induced impaired glucose metabolism remains controversial. Pharmacovigilance evaluations using spontaneous reporting systems are useful for analyzing drug‐related adverse events in clinical settings. Therefore, we conducted signal detection analyses for BCR‐ABL inhibitor‐induced impaired glucose metabolism by using the FDA Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) database. Signals for an increased reporting rate of impaired glucose metabolism were detected only for nilotinib use, whereas these signals were not detected for other BCR‐ABL inhibitors. Subgroup analyses showed a clearly increased nilotinib‐associated reporting rate of impaired glucose metabolism in male and younger patients. Although FAERS‐ and JADER‐based signal detection analyses cannot determine causality perfectly, our study suggests the effects on glucose metabolism are different between BCR‐ABL inhibitors and provides useful information for the selection of appropriate BCR‐ABL inhibitors.
Highlights
Chronic myeloid leukemia (CML) is a clonal stem cell neoplasm characterized by the presence of the Philadelphia (Ph) chromosome.[1]
The Reporting odds ratios (RORs) of impaired glucose metabolism associated with nilotinib was 1.26 in Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and 1.32 in the Japanese Adverse Drug Event Report (JADER) database, and signals for an increased reporting rate of impaired glucose metabolism were detected (P < 0.001)
In the JADER database, signals for an increased reporting rate of impaired glucose metabolism were detected in only the younger group treated with nilotinib (20‐60 s: ROR, 1.51, 95% confidence interval (CI), 1.127‐1.991; 70‐90 s: ROR, 1.11, 95% CI, 0.779‐1.550)
Summary
Chronic myeloid leukemia (CML) is a clonal stem cell neoplasm characterized by the presence of the Philadelphia (Ph) chromosome.[1] The Ph chromosome produces the breakpoint cluster region‐Abelson murine leukemia (BCR‐ABL) fusion protein, which dysregulates tyrosine kinase activity and induces uncontrolled proliferation of the granulocyte lineage. Nilotinib, dasatinib, bosutinib, and ponatinib are tyrosine kinase inhibitors that inhibit the activity of the BCR‐ABL fusion protein. These BCR‐ABL inhibitors have been reported to improve markedly the prognosis of CML.[2,3,4,5,6] maintaining high therapeutic adherence is necessary to obtain the maximum therapeutic effect with BCR‐ABL inhibitors.[7] For instance, an adequate blood concentration of imatinib is necessary to obtain the maximum therapeutic effect.[8] adverse events induced by BCR‐ABL inhibitors decrease therapeutic adherence. A good understanding of the adverse event profile of BCR‐ABL inhibitors is essential for successful CML treatment
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