Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a debilitating inflammatory disease associated with high recurrence rates and limited response to current therapies. Tezepelumab, a human monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), has emerged as a promising upstream biologic intervention. In the phase 3 WAYPOINT trial, tezepelumab significantly reduced nasal polyp score (-2.07), nasal congestion severity (-1.03), and SNOT-22 scores (-28.4), while decreasing the need for endoscopic sinus surgery by 98% versus placebo. Post hoc analyses of the NAVIGATOR trial showed SNOT-22 improvements (-21.06 vs -10.48 placebo), and PATHWAY data confirmed reductions in asthma exacerbations (up to 85%) and suppression of type 2 inflammatory biomarkers including eosinophils, FeNO, IL-5, and IL-13. Tezepelumab demonstrated a favorable safety profile without increased risk of serious infection or hypersensitivity. Although not approved for CRSwNP, tezepelumab is a promising investigational agent for patients with corticosteroid-refractory or biologic-insensitive disease. Ongoing trials such as ESSENCE will clarify its long-term efficacy, safety, and positioning relative to existing monoclonal antibodies.