Safety and Efficacy of Dupilumab, Omalizumab, and Mepolizumab in Moderate-to-Severe Asthma: A Systematic Review.

Biologic therapies such as dupilumab, omalizumab, and mepolizumab have significantly revolutionized the treatment options for moderate-to-severe asthma, particularly in patients with type 2 inflammation. This systematic review aims to compare the FDA black box warnings and safety profiles of these three biologics, emphasizing adverse event risks and clinical implications for practice. A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and FDA regulatory databases to identify studies published from December 2015 to April 2025. Eligible studies reported on adverse events, FDA black box warnings, or post-marketing surveillance related to the three biologics. Five independent researchers carried out data extraction and quality assessment in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A total of 24 studies met the inclusion criteria. Among the biologics, only omalizumab carries an FDA black box warning for anaphylaxis, necessitating heightened monitoring during initial administration. Dupilumab and mepolizumab demonstrated favorable safety profiles, with commonly reported events including injection-site reactions, transient eosinophilia, and conjunctivitis. Dupilumab was associated with the lowest rates of asthma exacerbations across various phenotypes. While all three biologics are effective in managing moderate-to-severe asthma, dupilumab and mepolizumab offer more favorable safety profiles. Clinicians should consider individual patient characteristics, phenotype, and prior adverse reactions when selecting biologic therapy. Awareness of FDA safety warnings is essential to optimize treatment decisions and ensure patient safety.