Post-marketing safety surveillance and signal characterization of the novel dissociative steroid Vamorolone in Duchenne muscular dystrophy: a comparative disproportionality analysis based on FAERS data.

Objective: To comprehensively evaluate the real-world post-marketing safety profile of the novel dissociative steroid Vamorolone and perform a comparative analysis against the traditional glucocorticoid deflazacort. Methods: Vamorolone-associated adverse event reports were extracted from the FAERS database (2023Q4-2025Q4) without indication restrictions to maximize detection sensitivity. Disproportionality analysis utilized ROR, PRR, BCPNN, and MGPS, reinforced by a strict Bonferroni correction to assess statistical robustness against multiple testing. Signal novelty was systematically assessed against the official FDA prescribing information. Temporal onset was evaluated via the Weibull distribution. To rigorously compare safety profiles across skeletal, growth, endocrine, and psychiatric domains, an exploratory head-to-head analysis was conducted using 2 × 2 contingency tables to calculate crude odds ratios against deflazacort. Results: We identified 1,171 cases (97.0% explicitly confirmed for muscular dystrophy) comprising 2,860 reported adverse events. Multi-algorithm consensus screening yielded a final refined cohort of 60 potential adverse event signals, predominantly concentrated within psychiatric disorders, investigations, and infections. Label cross-referencing revealed known risks (e.g., stubbornness, EBGM = 163.78 and acute adrenocortical insufficiency, EBGM = 71.14) and potentially novel signals (e.g., enuresis, EBGM = 42.40 and troponin I increased, EBGM = 39.54) that maintained statistical robustness under the stringent Bonferroni threshold. AEs exhibited an "early failure" onset (β = 0.74), particularly rapid for psychiatric events (median 36.5 days, β = 0.57). Comparatively, Vamorolone showed significantly lower reporting odds than deflazacort for growth retardation (Crude OR = 0.15, P = 0.003), osteoporosis (Crude OR = 0.27, P = 0.02), and femur fracture (Crude OR = 0.38, P = 0.008), while psychiatric signals remained comparable (P > 0.05). Conclusion: Exploratory analyses generate the hypothesis that Vamorolone may be associated with lower reporting odds for skeletal and growth-related adverse events compared to deflazacort. Nevertheless, known risks and unexpected hypothesis-generating signals-such as notable HPA axis suppression and early-onset psychiatric disturbances-remain critical safety concerns. Clinicians should interpret these differential reporting patterns with caution and rigorously monitor neurobehavioral and adrenal health during the first three months, with further external validation warranted.