Emerging pharmacotherapies in chronic rhinosinusitis with nasal polyps

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic, heterogeneous inflammatory disorder of the sinonasal mucosa that substantially impairs quality of life. It is characterized by T2 or non-T2 inflammatory endotypes and often coexists with asthma or aspirin-exacerbated respiratory disease, complicating management due to high recurrence rates and limited disease-modifying options. AREAS COVERED: This review evaluates emerging pharmacotherapies for CRSwNP, emphasizing targeted biologics developed from mechanistic understanding of inflammatory pathways. Approved monoclonal antibodies, dupilumab, omalizumab, and mepolizumab, are discussed regarding their effects on nasal polyp size, symptom relief, and patient-reported outcomes, with reference to comparative efficacy and safety. Evidence is drawn from RCTs, meta-analyses, and real-world studies, highlighting both clinical benefits and current limitations. Emerging therapies targeting upstream epithelial cytokines (TSLP, IL-33) and complementary strategies, including small-molecule inhibitors, microbiome modulation, and advanced topical delivery systems, are also addressed. EXPERT OPINION: Biologics have transformed CRSwNP treatment, but challenges remain in cost, treatment duration, and patient selection. Integrating endotype characterization, biomarkers, and comparative effectiveness data is crucial for personalized management. Future advances are expected from upstream immune modulation, restoration of epithelial barrier integrity, and optimized local drug delivery, enabling mechanism-based, adaptive approaches that maximize efficacy while minimizing systemic exposure.