Work

SUN-558 Multiple or Single Endocrine Abnormalities Associated with ImmuneCheckpoint Inhibitors

Year: 2025

Type: article

Abstract: Disclosure: F. Kamitani: Dainippon Sumitomo, Sanofi, Kyowa Kirin. Y. Nishioka: Novo Nordisk, Sanofi, Daiichi Sankyo, DeSC Healthcare. H. Nakajima: None. Y. Kurematsu: None. S. Okada: Mitsubishi Tanabe, ONO-Pharma, Eli Lilly & Company, Dainippon Sumitomo, Takeda, AstraZeneca, Novo Nordisk, Novo Nordisk, Mochida Pharmaceutical, Kyowa Kirin, Terumo. T. Myojin: None. T. Noda: None. T. Imamura: None. Y. Takahashi: Novo Nordisk, Recordati, Dainippon Sumitomo, Eli Lilly & Company, ONO-Pharma, Novartis Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Kyowa Kirin. Context: Although multiple endocrine abnormalities have been observed in patients treated with immune checkpoint inhibitors (ICIs), their pathophysiology has not been fully elucidated. Objective: To clarify the incidence, risk factors, and effect of multiple endocrine abnormalities on the overall survival (OS) in patients treated with ICI. Methods: We analyzed 12,978 patients treated with ICI using a Japanese administrative claims database including 12.4 million patients. Endocrine abnormalities were defined by hormone replacement therapy of levothyroxine and hydrocortisone for thyroiditis and hypophysitis/adrenalitis, respectively. More than 90% of ICI-related adrenal insufficiency has reportedly been associated with hypophysitis; therefore, most adrenal insufficiency was considered to represent hypophysitis. ICI-related type 1 diabetes (T1DM) was defined by insulin administration and a specific self-injection fee for T1DM. Kaplan-Meier analysis and Cox regression analysis adjusting for the number of ICI administrations and duration were performed to assess the effect of endocrine abnormalities on OS. Results: Hypothyroidism, adrenal insufficiency, and T1DM were observed in 10.5%, 4.6%, and 0.6% of patients, respectively. Multiple endocrine abnormalities were observed in 1.4%, and the most common combination was hypothyroidism and adrenal insufficiency (1.3%), followed by hypothyroidism and T1DM (0.07%), adrenal insufficiency and T1DM (0.02%), and triple hypothyroidism, adrenal insufficiency, and T1DM (0.02%), respectively. Among 12,978 patients treated with ICIs, 4,738 patients (36.5%) died during the observation period. In single abnormality, we found better survival in the order of patients with hypothyroidism and adrenal insufficiency than those without (P < .01). However, these analyses cannot exclude immortal time bias; therefore, we performed multivariable analysis. Convincingly, it still showed that the development of adrenal insufficiency and hypothyroidism was associated with lower mortality than none (adjusted hazard ratio [aHR] 0.60 and 0.65, respectively). Next, we compared patients with single and multiple endocrine abnormalities. Kaplan-Meier analysis showed better survival in patients with single and multiple endocrine abnormalities than in those without them (P < .01). Multivariable analysis also showed lower mortality in patients with single and multiple endocrine abnormalities groups (aHR 0.65; 95%CI, 0.58-0.72, P < .01; aHR 0.39; 95% CI, 0.28-0.54, P < .01, respectively) than in those without them. In addition, mortality was significantly lower in patients with multiple group than in single group (aHR 0.56; 95% CI, 0.39-0.79, P < .01). Conclusion: The development of multiple endocrine abnormalities was associated with superior survival compared with that of a single abnormality in patients treated with ICI. Presentation: Sunday, July 13, 2025

Source: Journal of the Endocrine Society

DOI: 10.1210/jendso/bvaf149.1210