国内医薬品副作用データベースに基づく分子標的抗がん薬による甲状腺機能障害の発現状況評価

抄録

Thyroid dysfunction, occurring as a side effect of treatment with molecular targeted antineoplastic drugs, should be monitored in patients. This study evaluated the occurrence of thyroid dysfunction as a result of treatment with 16 such drugs, using the Japanese Adverse Drug Event Report database. The reporting odds ratios indicated that thyroid dysfunction was associated with the use of the drugs sunitinib (SUN), ipilimumab (Ipi), nivolumab (Nivo), and pembrolizumab (Pembro). The median time to onset of hypothyroidism/hyperthyroidism from the beginning of treatment with SUN, Ipi, Nivo, and Pembro was 15/22.5, 34/36, 85/29, and 75.5/28 days, respectively. In the cases of Nivo and Pembro, hyperthyroidism occurred much earlier than hypothyroidism did. The Weibull distribution for SUN exhibited a profile for early failure, suggesting a high incidence of hypothyroidism, early in the course of treatment. Keeping these characteristics in mind, it is important to monitor thyroid function from the start of treatment with SUN. The maximum time for onset of thyroid dysfunction, from the end of therapy with SUN, Ipi, Nivo, and Pembro, was 1311, 295, 272, and 121 days, respectively. Thyroid dysfunction that developed during the course of treatment was surmised to occur as a result of the drug main effect and the immune response it elicited.

Thyroid dysfunction, caused by the therapeutic administration of molecular targeted antineoplastic drugs, is associated with various developmental situations. Therefore, thyroid function should be closely monitored, keeping in mind the properties of the drug and the profile of the patient.