Immunotherapy in Chronic Rhinosinusitis: Current Perspectives

Abstract

Background: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease of the upper airways that affects approximately 10–12% of the population and imposes a substantial clinical and socioeconomic burden. A considerable proportion of patients—particularly those with chronic rhinosinusitis with nasal polyps (CRSwNP)—exhibit persistent symptoms and frequent recurrences despite optimal conventional therapy, including intranasal corticosteroids, systemic corticosteroids, antibiotics, and functional endoscopic sinus surgery. Advances in endotype-driven research have identified type 2 (T2) inflammation, characterized by eosinophilia, elevated IgE, and activation of IL-4, IL-5, and IL-13 pathways, as a central mechanism underlying disease severity and treatment resistance.

Objective: This narrative review aims to synthesize current evidence on immunotherapeutic strategies in CRS, with particular emphasis on biologic therapies, and to evaluate their mechanisms of action, clinical efficacy, safety profiles, and role in personalized disease management.

Methods: A comprehensive review of the contemporary literature was conducted, focusing on randomized controlled trials, real-world observational studies, and international guideline recommendations addressing allergen immunotherapy (AIT) and biologic agents targeting key mediators of T2 inflammation.

Results: AIT remains the only disease-modifying treatment for patients with allergic CRS, demonstrating sustained symptom reduction and improved postoperative outcomes in appropriately selected individuals. Biologic therapies have fundamentally transformed the management of moderate-to-severe, uncontrolled CRSwNP. Agents targeting IL-4/IL-13 (dupilumab), IL-5 or its receptor (mepolizumab, benralizumab), IgE (omalizumab), and upstream epithelial alarmins such as thymic stromal lymphopoietin (tezepelumab) consistently reduce nasal polyp burden, improve sinonasal symptoms and olfactory function, decrease reliance on systemic corticosteroids, and lower the need for revision surgery. These therapies show favorable safety and tolerability profiles and provide clinically meaningful benefits across a broad spectrum of T2-driven endotypes.

Conclusions: Immunotherapy has emerged as a cornerstone of modern CRS management, enabling a shift from symptom-based treatment toward targeted, mechanism-driven interventions. Biologic therapies offer substantial benefits for patients with severe or refractory CRSwNP and represent a major advance toward precision medicine. Future priorities include refinement of predictive biomarkers, optimization of biologic selection and sequencing, and integration of immunotherapy into individualized, endotype-guided treatment algorithms.