Impact of dose and administration schedule on biologic efficacy in chronic rhinosinusitis with nasal polyps: a...

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.

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.

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 ( $\left(I^2=68.9\%\right)$ networks, whereas the UPSIT network demonstrated minimal heterogeneity $(I^2=7.5\%$ ) and remained statistically consistent.

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.