Abstract
Background: Trelegy Ellipta is a widely prescribed triple inhaler therapy for chronic obstructive pulmonary disease (COPD). Although its clinical efficacy is well established, evidence on sex-specific differences in adverse event (AE) profiles from real-world pharmacovigilance data remains limited. In addition, some AEs may reflect underlying disease characteristics rather than drug exposure, which complicates interpretation of safety signals. Objective: To explore sex-related differences in AEs associated with Trelegy Ellipta using the FDA Adverse Event Reporting System (FAERS). The study aimed to identify potential safety signals while accounting for alternative explanations, including comorbidity burden and disease-related variation. Methods: We retrospectively analyzed FAERS reports from January 2018 to April 2025, identifying 4555 AEs attributed to Trelegy Ellipta. Events were coded by System Organ Class (SOC) and stratified by patient sex. Frequencies were compared between male (n = 1621) and female (n = 2934) patients using chi-square tests, and associations were expressed as reporting odds ratios (RORs) with 95% confidence intervals (CIs). Results: Male patients more frequently reported hypertension (63.4% vs. 47.0%; p = 0.01), pneumonia (87.8% vs. 76.8%; p < 0.001), anxiety (91.0% vs. 66.9%; p < 0.001), sleep disorders (20.1% vs. 6.8%; p < 0.001), and hyperglycemia (92.7% vs. 52.1%; p < 0.001). Female patients more often reported headache (56.7% vs. 32.6%; p < 0.001), depression (33.1% vs. 9.0%; p < 0.001), and osteoporosis (41.7% vs. 2.4%; p < 0.001). Further variation was observed across neurological, musculoskeletal, and respiratory categories, suggesting a multidimensional pattern of sex differences. Conclusions: This FAERS-based analysis indicates distinct sex-specific safety signals for Trelegy Ellipta, particularly in cardiovascular, neuropsychiatric, and steroid-related domains. These findings are hypothesis-generating and highlight the importance of incorporating sex-disaggregated analyses into future pharmacovigilance and clinical studies.