The biologics dupilumab, mepolizumab, and omalizumab have recently been approved by the Food and Drug Administration (FDA) for chronic rhinosinusitis with nasal polyps, and their use in the clinical practice has been increasing. The safety profiles of these biologic therapeutics have been investigated in clinical trials. However, as clinical trials are performed in controlled settings that do not completely match regular use, real-world data are needed to further elucidate the exact adverse event profiles of these biologics.
During the 2024 American Rhinologic Society (ARS) meeting at the COSM that took place on May 15–16, 2024 in Chicago, Radhika Duggal, MA from Cleveland Clinic Lerner College of Medicine presented an analysis of the FDA Adverse Event Reporting System (FAERS) comparing the adverse event profiles of dupilumab, mepolizumab, and omalizumab.
The FAERS contains reports of adverse events and medical errors, with the administration of both small molecule drugs and biologic therapeutics, that have been submitted to the FDA. The authors of this study queried the FAERS for adverse events reported with dupilumab, mepolizumab, or omalizumab administration that had occurred in adults between the first quarter of 2019 and second quarter of 2023. Then, they compared the type and severity of categorized adverse events among the different biologics and used multiple regression modeling to identify predictors of severe adverse events.
Overall, the authors found approximately 79,000 adverse event logs, reflecting approximately 226,000 individual adverse reactions. The percentage of adverse event logs categorized as “serious” was 13% for dupilumab, 55% for mepolizumab, and 54% for omalizumab. Interestingly, there were differences in the types of individual adverse reactions most frequently reported for the three biologics. For dupilumab, most individual adverse reactions were dermatologic (24%) or administration/medical error-related (19%). The most reported individual adverse reactions for mepolizumab were administration/medical error-related (20%) or pulmonary (19%). For omalizumab, the most frequently reported individual adverse reactions were multisystem/not elsewhere classified (19%) or administration/medical error-related (14%).
The authors also found differences in the odds of reporting severe adverse events depending on the used biologic and patient age and sex. The odds of a reported severe adverse event were higher with mepolizumab (OR 3.61, 95% CI 3.29–3.98) and omalizumab (OR 15.33, 95% CI 13.98–16.81) than with dupilumab use. Even though adverse events were more commonly reported in females, the odds of a severe adverse event were 15% higher in males (OR 1.17, 95% CI 1.12–1.23). In addition, the odds of a severe adverse event rose by 26% with each 10-year increase in age (OR 1.26, 95% CI 1.24–1.28).
Overall, the authors found differences in the adverse event profiles of biologics that have been FDA-approved for chronic rhinosinusitis with nasal polyps. Moreover, the biologic type, prescription indication, and age and sex of the patient were identified as predictors of the risk of developing a severe adverse event. These data may have implications for the selection of a biologic by healthcare providers. Moreover, they can be helpful for educating patients regarding the risk of adverse events with biologic treatment.
Radhika Duggal emphasized that, as the current study was limited to adverse events reported in the FAERS, future large prospective studies will be needed to further elucidate the safety profiles of biologic therapeutic products for chronic rhinosinusitis with nasal polyps. Nevertheless, the findings of the current study suggest that the prescription indications and comorbidities of each patient should be considered when deciding which biologic to prescribe. Moreover, health care providers may use them when counseling and educating their patients regarding the risk of potential adverse events with biologic use.