Risk of developing hypothyroidism with the use of tyrosine kinase inhibitors and immune checkpoint inhibitors

Background: The survival rate of patients with cancer has been increasing because of the sustained anticancer effect of new drugs, such as immune checkpoints inhibitors (ICI). Unlike the existing cytotoxic chemotherapies, immunotherapy causes immune system disturbance, such as hypothyroidism. Comparative studies on hypothyroidism following administration of ICI alone and in combination with other drugs are scarce. Therefore, we investigated the incidence of hypothyroidism after ICI in patients with cancer using a national population-based database. Methods: Using the claims data from the Health Insurance Review and Assessment service in Korea, we retrospectively investigated patients with cancer who received chemotherapy between January 1, 2014 and February 28, 2021. Results: Of all patients with cancer (n = 665,445) who received all kinds of chemotherapy, those who have received ICI accounted for 1.91 %. Compare with cytotoxic chemotherapy and angiogenesis inhibitors (AIs), ICI was associated with earlier (236.1 ± 248.4 vs. 811.1 ± 661.7, P < 0.01) and more frequent (7.7 % vs. 4.4 %, P < 0.01) occurrence of hypothyroidism, as well as an increased risk of developing hypothyroidism (odds ratio [OR] 1.69, 95 % confidence interval [CI] 1.58–1.80). However, the incidence of grade 2 or higher hypothyroidism was similar in both groups of patients who received ICI (3.3 %) and AI (3.1 %). The incidence of hypothyroidism was 4.4 times higher in patients who received both AI and ICI than in those who were treated with ICI alone (OR 4.41, 95 % CI 3.40–5.71). Conclusions: This study showed a synergistic effect in patients who received multiple administrations of a drug that might be associated with thyroid dysfunction. Therefore, special attention should be paid to the treatment-related side effects when using drugs, such as AIs, concomitant with ICI treatment.