Immune checkpoint inhibitor-related endocrinopathies: A nationwide population-based study.

Abstract

2653 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, unleashing the body’s immune system against cancer is not without consequences and may trigger immune-related adverse events (irAEs), such as endocrinopathies. Real-world data of these endocrinopathies is lacking. This study aims to obtain the prevalence of endocrine irAEs and identify possible underlying demographic risk factors or disparities. Methods: A cross-sectional study was performed using a US-based population database (Explorys) that aggregates records from 26 healthcare systems and includes over 79 million patients. Our sample included all patients on an ICI, and we further identified patients who developed endocrinopathies while on different ICI regimens. The demographic data extracted was categorical, hence presented as counts and percentages. The odds ratio (OR), standard error, and 95% confidence interval were calculated with the use of SPSS software version 28.0 (IBM). Results: There were 20,950 patients on an ICI; 58% males, 83% Caucasians, 10% African-Americans (AA), 38% aged between 18-65, and 63% were over 65 years. The prevalence of the studied endocrinopathies is listed in the table. The most prevalent ICI-induced endocrinopathy was hypothyroidism (7.9-13%). Combination therapy with ipilimumab and nivolumab showed the highest prevalence of ICI-induced endocrinopathies, followed by durvalumab. The odds of developing ICI-induced endocrinopathy were significantly higher with combination therapy than nivolumab monotherapy (OR 1.6; 95% CI 1.4-1.9). There was no statistically significant difference in endocrinopathy prevalence when comparing Caucasians to AA and adults18-65 years to seniors over 65 years. Conclusions: This is the largest epidemiological study of ICI-related endocrinopathies. We find an intriguing divergence from endocrinopathy prevalence reported in the literature and real-world data we are presenting here. Over diagnosis of overt hypothyroidism, as opposed to subclinical hypothyroidism, is concerning as the former necessitates levothyroxine therapy. More alarming is the under diagnosis of hypopituitarism and PAI, in which delay in treatment can be fatal. The diagnosis of these conditions can be challenging. Raising awareness, setting protocols for testing, and involving endocrinologists are crucial. Further studies are needed to clarify our findings. [Table: see text]