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.
Yukesh et al. (Thu,) studied this question.