DETECTING SAFETY SIGNALS OF BILE ACID THERAPEUTICS: A FDA FAERS-BASED PHARMACOVIGILANCE STUDY
Author(s)
Zhanghe Chen1, Xiaomo (Shawn) Xiong, MS, PhD2, Jeff Jianfei Guo, BPharm, PhD3;
1University of Cincinnati, Research Assistant, Cincinnati, OH, USA, 2James L Winkle College of Pharmacy, University of Cincinnati, Blue Ash, OH, USA, 3James L Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, USA
1University of Cincinnati, Research Assistant, Cincinnati, OH, USA, 2James L Winkle College of Pharmacy, University of Cincinnati, Blue Ash, OH, USA, 3James L Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, USA
OBJECTIVES: Bile acid therapeutics are used for bile acid diseases involving disorders bile acid synthesis, metabolism, or intestinal absorption. Chenodiol (Ctexli), a synthetic bile acid, recently repurposed to treat cerebrotendinous xanthomatosis (CTX) in adults, has a limited well-defined real world safety data. This study analyzed and characterized the safety profile of chenodiol and compared with other bile acid medications.
METHODS: The adverse events report of study drugs including chenodiol, colestipol, cholestyramine, and colesvelam were extracted from the FDA Adverse Event Reporting System (FAERS) from 2012 to 2025 and identified by both generic and brand names. Adverse events of interests were analyzed and categorized using preferred terms and system organ class. Safety signals were evaluated using established criteria based on the reporting odds ratio (ROR) and proportional reporting ratio (PRR), each with 95% confidence intervals, along with the chi-square statistic (χ²) and p-values, with signals defined as ROR and PRR > 2, a lower 95% CI bound > 1, χ² ≥ 3, and p < 0.005.
RESULTS: Disproportionality analysis identified potential safety signals associated with chenodiol, cholestyramine, colesevelam, and colestipol. Among the four-bile acid-related agents, chenodiol was the only drug demonstrating statistically robust and consistent safety signals across all predefined criteria. The strongest signal was observed for hepatic enzyme increased, which showed markedly elevated reporting (ROR, 21.92 [95% CI, 13.89-34.58]; PRR, 19.92 [95% CI, 13.17-30.13]; χ² = 349.56). Additional confirmed signals for chenodiol included vomiting (ROR, 4.30 [95% CI, 2.74-6.73]; PRR, 4.23 [95% CI, 2.72-6.57]; χ² = 44.99) and diarrhea (ROR, 2.42 [95% CI, 1.76-3.33]; PRR, 2.41 [95% CI, 1.76-3.29]; χ² = 30.51).
CONCLUSIONS: Chenodiol’s recent approval for cerebrotendinous xanthomatosis exemplifies how existing medications can be re-evaluated for new indications, and other therapeutic options. Integrating real-world safety data from post-marketing surveillance is crucial to supporting these repurposing efforts and ensuring patient safety.
METHODS: The adverse events report of study drugs including chenodiol, colestipol, cholestyramine, and colesvelam were extracted from the FDA Adverse Event Reporting System (FAERS) from 2012 to 2025 and identified by both generic and brand names. Adverse events of interests were analyzed and categorized using preferred terms and system organ class. Safety signals were evaluated using established criteria based on the reporting odds ratio (ROR) and proportional reporting ratio (PRR), each with 95% confidence intervals, along with the chi-square statistic (χ²) and p-values, with signals defined as ROR and PRR > 2, a lower 95% CI bound > 1, χ² ≥ 3, and p < 0.005.
RESULTS: Disproportionality analysis identified potential safety signals associated with chenodiol, cholestyramine, colesevelam, and colestipol. Among the four-bile acid-related agents, chenodiol was the only drug demonstrating statistically robust and consistent safety signals across all predefined criteria. The strongest signal was observed for hepatic enzyme increased, which showed markedly elevated reporting (ROR, 21.92 [95% CI, 13.89-34.58]; PRR, 19.92 [95% CI, 13.17-30.13]; χ² = 349.56). Additional confirmed signals for chenodiol included vomiting (ROR, 4.30 [95% CI, 2.74-6.73]; PRR, 4.23 [95% CI, 2.72-6.57]; χ² = 44.99) and diarrhea (ROR, 2.42 [95% CI, 1.76-3.33]; PRR, 2.41 [95% CI, 1.76-3.29]; χ² = 30.51).
CONCLUSIONS: Chenodiol’s recent approval for cerebrotendinous xanthomatosis exemplifies how existing medications can be re-evaluated for new indications, and other therapeutic options. Integrating real-world safety data from post-marketing surveillance is crucial to supporting these repurposing efforts and ensuring patient safety.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
RWD23
Topic
Real World Data & Information Systems
Disease
SDC: Gastrointestinal Disorders, SDC: Rare & Orphan Diseases