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.
Keywords: Chronic rhinosinusitis with nasal polyps; SNOT-22; asthma comorbidity; biologic therapy; endoscopic sinus surgery; tezepelumab.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a long-lasting inflammatory condition of the sinuses that causes nasal blockage, loss of smell, facial pressure, and poor quality of life. Current treatments, such as corticosteroid sprays, oral steroids, and sinus surgery, are often not effective in patients with severe or recurrent disease. Tezepelumab is a new investigational medicine designed to target thymic stromal lymphopoietin (TSLP), an important signaling protein that starts inflammation in the sinuses. By blocking TSLP, tezepelumab works “upstream” to reduce multiple inflammatory pathways involved in CRSwNP. In a large clinical study called the WAYPOINT trial, patients receiving tezepelumab showed significant reductions in nasal polyp size and nasal blockage compared with placebo, along with major improvements in quality of life and smell. Tezepelumab also reduced the need for sinus surgery by 98% and lowered the need for oral steroids by 88%. Findings from earlier studies, including the NAVIGATOR and PATHWAY trials, showed similar benefits in patients who also had both asthma and CRSwNP diagnoses. Tezepelumab has been well tolerated in studies, with no major safety concerns reported. While it is not yet approved for CRSwNP, ongoing research continues to evaluate its long-term benefits, safety, and role compared with existing treatments.