Real-world evidence of the incidence of and risk factors for T1DM and hypothyroidism as immune-related adverse events associated with programmed cell death-1 inhibitors

Abstract Objectives The incidence of type 1 diabetes mellitus (T1DM) and hypothyroidism as immune-related adverse events (irAEs) after programmed cell death-1 inhibitor (PD-1i) administration has not yet been sufficiently evaluated in a real clinical setting. To assess the incidence of T1DM and hypothyroidism among PD-1is and to identify the risk factors associated with hypothyroidism using a large claims database. Methods This cohort study utilized the Shizuoka Kokuho database in Japan from 2012 to 2018, including approximately 2.2 million people. We enrolled 695 PD-1i-treated patients. T1DM and hypothyroidism as irAEs were identified using ICD-10 and Anatomical Therapeutic Chemical classification codes. Risk factors for hypothyroidism were explored by the multivariable Fine and Gray regression model after adjusting for age group and sex, treating death as a competing risk. Results The cumulative incidences of T1DM and hypothyroidism were 0.3% and 8.3%, respectively. We described the detailed onset timing of irAEs in T1DM and hypothyroidism; hypothyroidism was observed evenly within one year of PD-1i prescription. Sex and certain cancer types, such as lung and urothelial cancer, were significantly associated with the sub-distribution hazard ratio (sHR) (female: sHR, 2.04 [95% confidence interval (CI), 1.20-3.47]; lung cancer: sHR, 0.55 [95% CI, 0.32-0.95]; urothelial carcinoma: sHR, 2.40 [95% CI, 1.05-5.49]). Conclusions The incidence of T1DM and hypothyroidism as irAEs and the associated risk factors identified in this analysis were comparable to those found in previous studies. Using a large claims database to detect irAEs, such as T1DM and hypothyroidism, may lead to the safer use of PD-1is.