Impact of dose and administration schedule on biologic efficacy in chronic rhinosinusitis with nasal polyps: a network meta-analysis

Objective Chronic rhinosinusitis with nasal polyps (CRSwNP) severely impairs quality of life despite standard surgical and medical therapies. We conducted a network meta-analysis to compare the relative efficacy of biologic agents targeting type 2 inflammation, with a specific focus on how dose and administration frequency influence patient-reported and objective outcomes. Methodology/Principal A frequentist network meta-analysis was performed across randomized controlled trials evaluating dupilumab, omalizumab, mepolizumab, and benralizumab versus placebo in adults with CRSwNP. Primary outcomes evaluated included sinonasal quality of life (Sino-Nasal Outcome Test-22 [SNOT-22]), objective polyp burden (Nasal Polyp Score [NPS]), and olfactory function (University of Pennsylvania Smell Identification Test [UPSIT]). Interventions were ranked using P-scores. Results Sixteen randomized controlled trials (4,861 patients) were included. Dupilumab (600 mg loading dose followed by 300 mg every 1–2 weeks) ranked as the most effective regimen for improving quality of life (P-score = 0.907) and provided the greatest enhancement in olfactory function (P-score = 0.006; Standardized Mean Difference [SMD] = 1.91, 95% confidence interval [CI]: 1.24–2.59). Conversely, benralizumab 30 mg administered every 4 weeks was the top-ranked intervention for reducing objective polyp burden (P-score = 0.864). Substantial heterogeneity and significant global inconsistency were observed within the SNOT-22 ( I 2 = 86.5 % ) and NPS ( I 2 = 68.9 % networks, whereas the UPSIT network demonstrated minimal heterogeneity ( I 2 = 7.5 % ) and remained statistically consistent. Conclusion Biologic efficacy in CRSwNP varies distinctly by clinical endpoint and dosing frequency. Dupilumab optimally drives patient-reported quality of life and olfactory recovery, while intensive benralizumab dosing (every 4 weeks) provides the greatest objective reduction in nasal polyp burden. Therapeutic selection should be personalized to align with individual patient phenotypes and clinical priorities.