Osilodrostat Safety Profile: Findings from Real-World Data in the FAERS Database.

Background/

Objectives

Cushing's syndrome (CS), including Cushing's disease (CD)-the most common type-has a substantial negative impact on morbidity, mortality, and patients' quality of life. Medical management of CS is essential for controlling hypercortisolism as part of preoperative preparation for definitive surgical treatment and for managing residual or relapsed hypercortisolism post-surgery. Osilodrostat, a dual inhibitor of glucocorticoid and mineralocorticoid biosynthetic pathways, has been approved for the medical treatment of CS since early 2020. However, real-world data on its adverse effects remain limited. We mined the FAERS database and analyzed the reports associated with osilodrostat up to 1 October 2024.

Methods

Descriptive and disproportionality methods based on Relative Odds Ratio (ROR), Chi-square (χ2), and Proportional Reporting Ratio (PRR), were used to discern potential safety signals and assess the significance of osilodrostat-associated adverse events.

Results

This study identified 782 reports in which osilodrostat was the primary suspected drug, containing 593 preferred terms (PTs) and 2481 occurrences. The most frequently registered events belonged to the following SOCs: "General disorders and administration site conditions" (n = 457, 18.4%), "Injury, poisoning and procedural complications" (n = 311, 12.5%), "Gastrointestinal disorders" (n = 278, 11.2%), "Investigations" (n = 260, 10.5%), and "Nervous system disorders" (n = 184, 7.4%). Among PTs, off-label use was the most commonly reported, aligning with the fact that the vast majority of cases originated from the U.S. (84%), where osilodrostat is officially approved only for the treatment of CD. Disproportionality analysis confirmed previously known and new potential adverse drug reactions associated with osilodrostat treatment, including reports of cardiac flutter (n: 4; PRR: 19.42; χ2: 49.57), ventricular extrasystoles (n: 4; PRR: 11.85; χ2: 29.62), muscular weakness (n: 8; PRR: 2.25; χ2: 4.38), rib fracture (n: 4; PRR: 6.66; χ2: 13.99), spinal fracture (n: 3; PRR: 4.66; χ2: 5.35), sepsis (n: 9; PRR: 2.63; χ2: 7.56), fungal infections (n: 4; PRR: 3.67; χ2: 5.33), and COVID-19 (n: 32; PRR: 5.07; χ2: 101.16).

Conclusions

This study highlights new risks and offers valuable insights into osilodrostat use; however, further research and validation are necessary, particularly for adverse reactions not yet explicitly documented in the summary of product characteristics.