Interstitial lung disease associated with antiandrogen agents: a pharmacovigilance study based on FDA adverse event...

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).

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.

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.

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.