As allergists, we are increasingly managing patients with chronic rhinosinusitis with nasal polyps (CRSwNP)—a condition driven by Type 2 inflammation that often coexists with asthma, aspirin-exacerbated respiratory disease (AERD), and allergic rhinitis. While Dupilumab has been a major breakthrough, we continue to see a subset of patients with suboptimal responses or contraindications to currently approved biologics.
Tezepelumab (Tezspire®), a monoclonal antibody targeting TSLP (thymic stromal lymphopoietin), offers a novel upstream mechanism that may expand our treatment arsenal for nasal polyposis.
The Role of TSLP in Type 2 Inflammation
TSLP is an epithelial-derived alarmin released in response to environmental and inflammatory triggers. It acts on multiple downstream pathways by activating dendritic cells, innate lymphoid cells (ILC2s), and promoting the differentiation of Th2 cells—thereby orchestrating the release of IL-4, IL-5, and IL-13.
This upstream activation makes TSLP a strategic target in polymorphic Type 2 conditions, such as:
Severe eosinophilic asthma
Nasal polyposis
Atopic dermatitis
Eosinophilic esophagitis
By blocking TSLP, tezepelumab inhibits both adaptive and innate Type 2 pathways, distinguishing it mechanistically from agents targeting IL-4Rα (Dupixent), IL-5 (Nucala, Fasenra), or IgE (Xolair).
Tezspire in CRSwNP: Clinical Evidence
While tezepelumab is currently FDA-approved for severe asthma, it is now being evaluated in Phase 3 trials for CRSwNP (e.g., the WAYPOINT study, NCT05553090).
Key endpoints include:
Change in nasal polyp score (NPS)
Lund-Mackay CT scores
Improvement in nasal congestion scores and sense of smell
Reduction in systemic corticosteroid use and surgical rescue rates
Early results from asthma trials (e.g., NAVIGATOR) have shown significant reductions in blood and sputum eosinophils, FeNO, and asthma exacerbation rates, regardless of baseline eosinophil count—suggesting potential benefit for patients with low eosinophil CRSwNP phenotypes as well.
Potential Role in Refractory Nasal Polyposis
As specialists, we encounter patients who:
Fail to respond adequately to Dupilumab
Experience adverse effects or contraindications to existing biologics
Have mixed inflammatory endotypes or uncertain biomarkers
Tezepelumab’s broader suppression of the inflammatory cascade makes it an intriguing candidate for such cases. Its mechanism may address both eosinophilic and non-eosinophilic CRSwNP endotypes, potentially offering improved outcomes in a wider population.
Administration and Practical Considerations
Tezspire is administered as a subcutaneous injection every 4 weeks, and is currently only available for healthcare professional administration, though at-home injection protocols are under evaluation.
As with other biologics, long-term safety, adherence, cost, and insurance coverage will be key considerations should it be approved for CRSwNP.
Conclusion
Tezepelumab represents a promising biologic that may shift our paradigm for treating nasal polyps—particularly in refractory, non-traditional, or steroid-dependent patients. As the results of ongoing trials emerge, we may soon have another evidence-based option that targets airway inflammation from its origin.
As always, patient selection, phenotype characterization, and biomarker profiling will be essential to integrating Tezspire effectively into clinical practice.
Tezspire Tezepelumab for Severe Asthma
Nasal Polyps Treatment; Past, Present and Future
Dr. Alan Khadavi is a board-certified allergist and immunologist based in Los Angeles, specializing in the diagnosis and treatment of chronic sinus disease, asthma, and allergic conditions.