2025, Vol. 7, Issue 1, Part F

Background: Allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyposis (CRSwNP) are highly prevalent inflammatory disorders of the upper airway. Intranasal corticosteroids (INCS) represent the first-line treatment for both conditions; however, head-to-head comparisons between fluticasone propionate (FP) and fluticasone furoate (FF) are scarce. FF possesses higher glucocorticoid receptor affinity and extended mucosal retention, potentially translating into faster and superior symptom control compared to FP. Nonetheless, the comparative efficacy and safety of these agents in AR and CRSwNP remain unclear.
Objective: To perform a simulated head-to-head meta-analysis comparing FP and FF in the management of AR and CRSwNP, evaluating clinical efficacy, rapidity of symptom relief, patient preference and polyp size reduction-surgery avoidance, and safety (epistaxis incidence).
Methodology: Hypothetical but realistic data were derived from four AR trials (total N=1,200), two CRSwNP trials (N=350), and five studies evaluating epistaxis risk (N=1,500). Outcomes included mean differences (MD) in reflective Total Nasal Symptom Score (rTNSS), time to symptom onset (days), patient preference (%), change in endoscopic polyp score, surgery avoidance rate (%), and relative risk (RR) for epistaxis. Standard meta-analytic techniques (fixed/random effects), estimation of heterogeneity (I²), and calculation of pooled effect sizes were employed. Published clinical and pharmacologic studies served as reference anchors
Results: In AR, FF reduced rTNSS by a pooled mean difference of -0.25 (±0.10; P=0.01; I²=45%) and expedited symptom relief by approximately 0.8 days (P=0.005; I²=30%) compared to FP. Patient preference favored FF significantly, with 58% opting for FF versus 27% for FP (difference +28%±6%; p<0.001; I²=20%). In CRSwNP, both agents showed comparable efficacy: polyp score change was negligible (MD +0.02; P=0.80; I²=0%), and surgery avoidance exhibited a minor, non-significant preference for FP (? +5%; P=0.45; I²=10%). Safety profiles were largely similar, with epistaxis risk ratio at 1.10 (±0.05; P=0.15; I²=25%).
Conclusion: Our simulated meta-analysis supports that FF offers modest but statistically significant benefits in AR including quicker symptom relief and stronger patient preference likely attributable to its pharmacologic profile and sensory advantages. In CRSwNP, FF and FP perform similarly in reducing polyp burden and avoiding surgery. Safety profiles overlap, with no appreciable difference in the risk of epistaxis. These findings suggest FF may be favored in AR for its patient-centered advantages, while either agent may be appropriate in CRSwNP. However, these modeled results should be confirmed by real-world, well-powered, head-to-head randomized trials with extended follow-up and quality-of-life and economic evaluations.