Interstitial lung disease associated with antiandrogen agents: a pharmacovigilance study based on FDA adverse event reporting system.
This study identified seven antiandrogens, including degarelix, with potential signals for interstitial lung disease, highlighting the need for further validation of these findings.
Where it sits
this study against the rest of the degarelix corpusSummary and findings
This study analyzed adverse event reports to detect potential signals of interstitial lung disease (ILD) associated with antiandrogen agents, including degarelix. A total of 761 cases were examined, identifying seven agents with positive ILD signals. The findings suggest a need for further validation of these signals.
Abstract
<h4>Background</h4>This study aims to detect potential signals of interstitial lung disease (ILD) associated with antiandrogen agents by employing a multi-algorithm, dual-level (Standardized MedDRA Query [SMQ] and Preferred Term [PT]) framework combined with the updated FDA Adverse Event Reporting System (FAERS) dataset (through 2024).<h4>Methods</h4>We analyzed data from the fourth quarter of 2003 through the fourth quarter of 2024. Disproportionality analysis employed four complementary methods: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM). Signals were evaluated at both the SMQ and PT levels.<h4>Results</h4>A total of 761 cases of ILD associated with antiandrogen agents were analyzed. We identified seven agents showing positive ILD signals in FAERS. They were apalutamide, bicalutamide, degarelix, darolutamide, flutamide, goserelin, and nilutamide. Among them, darolutamide stood out with a newly identified pharmacovigilance signal, whereas no such signal had been detected in prior FAERS analyses. Bicalutamide exhibited positive signals for both "Interstitial lung disease" and "Pulmonary fibrosis" at the PT level, a pattern not seen with the other drugs. Japan contributed the most reports (61.37%); death and hospitalization were the most common outcomes (54.80%). Female-related ILD reports were mainly observed with goserelin and leuprolide used for breast cancer.<h4>Conclusion</h4>This study identified seven antiandrogens with pharmacovigilance signals, among which the signal for darolutamide was detected for the first time. The dual-level analysis generated the hypothesis that bicalutamide-associated ILD may have a greater tendency to evolve into a fibrotic phenotype. The observed Japanese predominance in reporting likely reflects regulatory and reporting-related factors rather than a true biologic excess risk. Female-related ILD reports represent solely a signal-generating observation. These findings are exploratory and require further validation.
Background
This study addresses the potential association between interstitial lung disease (ILD) and antiandrogen agents, which has not been thoroughly investigated in prior literature. Previous analyses may not have detected signals for certain agents, highlighting the importance of ongoing pharmacovigilance. The study aims to utilize a comprehensive dataset to identify any new signals related to ILD.
Methods
The study employed a multi-algorithm, dual-level framework using the FDA Adverse Event Reporting System (FAERS) dataset from Q4 2003 to Q4 2024. Disproportionality analysis was conducted using four methods: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM). The analysis focused on both Standardized MedDRA Query (SMQ) and Preferred Term (PT) levels.
Results
A total of 761 cases of ILD associated with antiandrogen agents were identified. Seven agents were found to have positive ILD signals, including degarelix. Bicalutamide showed positive signals for both 'Interstitial lung disease' and 'Pulmonary fibrosis' at the PT level, which was not observed with other agents. The majority of reports originated from Japan, accounting for 61.37% of cases.
Interpretation
The findings suggest that while several antiandrogens are associated with ILD, the clinical significance of these signals varies. The signal for bicalutamide indicates a potential risk for pulmonary fibrosis, but the clinical implications remain uncertain. The predominance of reports from Japan may introduce bias, and the exploratory nature of the study necessitates further investigation to confirm these associations.
Key findings
- 761 cases of ILD associated with antiandrogen agents were analyzed.
- Seven agents showed positive ILD signals: apalutamide, bicalutamide, degarelix, darolutamide, flutamide, goserelin, and nilutamide.
- Bicalutamide exhibited positive signals for both 'Interstitial lung disease' and 'Pulmonary fibrosis' at the PT level.
- Japan contributed 61.37% of the reports.
- Death and hospitalization were the most common outcomes, reported in 54.80% of cases.
Limitations
- Exploratory findings requiring further validation.
- Predominance of reports from Japan may reflect reporting biases.
- Small sample size may limit generalizability.
- No direct clinical outcomes measured, only adverse event reports.