Abstract
AIM/INTRODUCTION: Although immune checkpoint inhibitor-related type 1 diabetes mellitus (ICI-T1DM) is a rare condition, it is of significant concern globally. We aimed to elucidate the precise incidence, risk factors, and impact of ICI-T1DM on survival outcomes. MATERIALS AND METHODS: The study is a large retrospective cohort study, performed using the DeSC Japanese administrative claims database comprising 11 million patients. The database population is reportedly similar to the entire population of Japan. Patients administered ICI between 2014 and 2022 were enrolled in the study, including 21,121 patients. The risk factors for ICI-T1DM development and their characteristics were evaluated by logistic regression analysis. Development of a new irAE after the day following the first administration of ICI was set as the study outcome. RESULTS: ICI-T1DM was observed in 102 (0.48%) of the 21,121 patients after ICI initiation. PD-(L)1 and CTLA-4 combination therapy was associated with an increased risk of ICI-T1DM compared with PD-1 monotherapy (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.21-4.58; P = 0.01). Patients with a prior diagnosis of diabetes mellitus (OR, 1.59; 95% CI, 1.03-2.46; P = 0.04) or hypothyroidism (OR, 2.48; 95% CI, 1.39-4.43; P < 0.01) also exhibited an increased risk of ICI-T1DM. The Kaplan-Meier analysis revealed that patients with ICI-T1DM showed higher survival rates than those without (log-lank test, P < 0.01). Multivariable Cox regression analysis demonstrated that ICI-T1DM development was associated with lower mortality (hazard ratio, 0.60; 95% CI, 0.37-0.99; P = 0.04). CONCLUSIONS: Collectively, the results of this study demonstrate the precise incidence and risk factors of ICI-T1DM. The development of ICI-T1DM, like other irAEs, is associated with higher survival rates.