PSAT122 The Changing Face of Drug-Induced Adrenal Insufficiency in the Food and Drug Administration Adverse Event Reporting System

Abstract

Abstract Importance: Adrenal insufficiency is a life-threatening condition complicating heterogenous disorders across various disciplines, with challenging diagnosis and a notable drug-induced component. Objective To describe the spectrum and main features of drug-induced adrenal insufficiency through adverse drug event reports received by the Food and Drug Administration (FDA). Design: We conducted a retrospective disproportionality analysis within one of the largest publicly accessible spontaneous reporting system. Setting The FDA Adverse Event Reporting System (FAERS) collecting more than 15 million reports. Participants: Adverse event reports extracted from FAERS over the past 2 decades (2000-2020), with a focus on the 2015-2020 period. Main Outcomes and Measures: Descriptive statistics were used to assess the reporting trend of drug-induced adrenal insufficiency. Cases were selected if they contained any of the preferred terms in the Medical Dictionary for Regulatory Activities describing adrenal hypofunctions. We computed the reporting odds ratio (ROR) with relevant 95% confidence interval (CI) using Bonferroni correction to identify signals of disproportionate reporting for drugs recorded in at least 10 cases as primary suspect. Results We identified 8,496 cases (5,282 in the 2015-2020 period), 97.5% being serious and 41.1% requiring hospitalization. We identified 56 drugs (out of 164) associated with significant disproportionality within various pharmacological classes: glucocorticoids (N=1971, constant over time), monoclonal antibodies (1,330 out of 1,644 cases with immune checkpoint inhibitors, reaching 76% in 2020), hormone therapy (N=291), anti-infectives (N=252), drugs used for hypercortisolism or adrenocortical cancer diagnosis and/or treatment (N=169), protein kinase inhibitors (N=138). Conclusions and Relevance This comprehensive insight into the evolution of drug-induced adrenal insufficiency highlighted the heterogeneous spectrum of culprit drugs classes, including the consolidated role of topical and systemic corticosteroids and the emerging increased reporting of immune checkpoint inhibitors. Targeted screening and educational programs are needed to urgently identify predictive factors. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.