Weight-related adverse events associated with asthma biologics: A disproportionality analysis of Food and Drug Administration adverse event reporting system data

Abstract Introduction: Biologic drugs have revolutionized the treatment of severe asthma. However, their long-term metabolic safety is not fully understood. Obesity and weight-related adverse events (AEs) are clinically important comorbidities in severe asthma, but randomized trials seldom capture these outcomes. As a result, postmarketing pharmacovigilance studies are critical for identifying the potential safety signals related to weight regulation in the real-world situations. Objectives: To evaluate disproportionality signals for weight-and appetite-related AEs associated with six biologics approved for asthma using the Food and Drug Administration Adverse Event Reporting System (FAERS) data. Methods: A retrospective case–noncase disproportionality analysis (DPA) was conducted using Individual Case Safety Reports from the FAERS, accessed through OpenVigil-FDA. Reports from database inception (~2004) to October 2025 were included. Omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab were assessed as primary suspect drugs. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated for predefined Medical Dictionary for Regulatory Activity preferred terms related to weight change, appetite, and metabolic outcomes. A signal of disproportionate reporting was defined as ROR >1, lower 95% CI >1, and ≥3 cases. Case-by-case analysis was not performed. Results: Strong positive signals for obesity and weight gain were observed for mepolizumab (obesity ROR 22.25, 95% CI 20.65–23.98), omalizumab, benralizumab, and tezepelumab. Dupilumab demonstrated consistently inverse associations for all weight-related outcomes, including obesity (ROR 0.10, 95% CI 0.07–0.14). Appetite-related events were generally nonsignificant across biologics. Conclusions: This DPA identified differential reporting patterns of weight-related AEs among asthma biologics. Findings are hypothesis-generating and likely influenced by confounding factors, particularly oral corticosteroid (OCS) exposure and indication bias. Careful metabolic monitoring and confirmatory pharmacoepidemiological studies are warranted to clarify causality and clinical relevance.