Abstract
Background
Treatment with tezepelumab has been effective for sinonasal symptoms in patients with severe, uncontrolled asthma and a history of chronic rhinosinusitis with nasal polyps, but its efficacy and safety in adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps is unknown.
Methods
We randomly assigned adults with physician-diagnosed, symptomatic, severe chronic rhinosinusitis with nasal polyps to receive standard care and either tezepelumab (at a dose of 210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. The coprimary end points were the changes from baseline in the total nasal-polyp score (range, 0 to 4 [for each nostril]; higher scores indicate greater severity) and the mean nasal-congestion score (range, 0 to 3; higher scores indicate greater severity) at week 52. Key secondary end points assessed in the overall population were the loss-of-smell score, the total score on the Sinonasal Outcome Test (SNOT-22; range, 0 to 110; higher scores indicate greater severity), the Lund–Mackay score (range, 0 to 24; higher scores indicate greater severity), the total symptom score (range, 0 to 24; higher scores indicate greater severity), and the first decision to treat with nasal-polyp surgery or use of systemic glucocorticoid therapy, or both, assessed in time-to-event analyses (individual and composite).
Research Summary
Tezepelumab for Severe Chronic Rhinosinusitis with Nasal Polyps
Results
In total, 203 patients were assigned to receive tezepelumab and 205 to receive placebo. At week 52, the patients who received tezepelumab had significant improvements in the total nasal-polyp score (mean difference vs. placebo, −2.07; 95% confidence interval [CI], −2.39 to −1.74) and the mean nasal-congestion score (−1.03; 95% CI, −1.20 to −0.86) (P<0.001 for both scores). Tezepelumab significantly improved the loss-of-smell score (mean difference vs. placebo, −1.00; 95% CI, −1.18 to −0.83), SNOT-22 total score (−27.26; 95% CI, −32.32 to −22.21), Lund–Mackay score (−5.72; 95% CI, −6.39 to −5.06), and total symptom score (−6.89; 95% CI, −8.02 to −5.76) (P<0.001 for all scores). Surgery for nasal polyps was indicated in significantly fewer patients in the tezepelumab group (0.5%) than in the placebo group (22.1%) (hazard ratio, 0.02; 95% CI, 0.00 to 0.09); there was significantly less use of systemic glucocorticoids with tezepelumab (5.2%) than with placebo (18.3%) (hazard ratio, 0.12; 95% CI, 0.04 to 0.27) (P<0.001 for both time-to-event analyses).
Conclusions
Tezepelumab therapy led to significantly greater reductions in the size of nasal polyps, the severity of nasal congestion and sinonasal symptoms, and the use of nasal-polyp surgery and systemic glucocorticoids than placebo in adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps. (Funded by AstraZeneca and Amgen; WAYPOINT ClinicalTrials.gov number, NCT04851964.)
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Tezepelumab for Chronic Rhinosinusitis with Nasal Polyps
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Notes
This article was published on March 1, 2025, and updated on March 27, 2025, at NEJM.org.
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
Supported by AstraZeneca and Amgen.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank the patients involved in this trial and their families, the investigators, the site staff, and the trial team; Karin Bowen, M.Sc., for contributions to the trial design and analyses; and Lisa Simpson, Ph.D., of PharmaGenesis London, for medical writing assistance with earlier versions of the manuscript.
Supplementary Material
Information & Authors
Information
Published In
New England Journal of Medicine
Volume 392 • Number 12 • March 27, 2025
Pages: 1178-1188
Copyright
Copyright © 2025 Massachusetts Medical Society. All rights reserved.
For personal use only. Any commercial reuse of NEJM Group content requires permission.
Translation
History
Published online: March 1, 2025
Published in issue: March 27, 2025
Topics
- Allergy
- Allergy/Immunology General
- Asthma (Allergy/Immunology)
- Asthma (Pulmonary/Critical Care)
- Autoimmune Disease
- Clinical Medicine General
- Inflammatory Disease
- Otolaryngology General
- Outpatient-Based Clinical Medicine
- Pulmonary/Critical Care General
- Rheumatology General
- T-Cells
Authors
Authors
Brian J. Lipworth, M.D.1, Joseph K. Han, M.D.2, Martin Desrosiers, M.D.3, Claire Hopkins, M.D., Ph.D.4, Stella E. Lee, M.D.5, Joaquim Mullol, M.D., Ph.D.6, Oliver Pfaar, M.D.7, Ting Li, Ph.D.8, Claudia Chen, M.Sc., M.P.H.9, Gun Almqvist, M.Sc.10, Mary Kay Margolis, M.P.H., M.H.A.11, Julie McLaren, M.D.12, Shankar Jagadeesh, Ph.D.13, Jamie MacKay, M.D., Ph.D.14, Ayman Megally, M.D., M.P.H.13, Åsa Hellqvist, M.Sc.15, Vaishali S. Mankad, M.D.8, Lila Bahadori, M.D.13, and Sandhia S. Ponnarambil, M.B., B.S.16, for the WAYPOINT Study Investigators*
Affiliations
1Scottish Centre for Respiratory Research, and ENT Rhinology Clinic, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom
2Department of Otolaryngology, Head and Neck Surgery, Eastern Virginia Medical School, Norfolk
3Division of Otolaryngology, Head and Neck Surgery, Centre Hospitalier de l’Université de Montréal, University of Montreal, Montreal
4Department of Otolaryngology–Head and Neck Surgery, Guy’s and St. Thomas’ Hospital, London
5Division of Otolaryngology, Head and Neck Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston
6Rhinology Unit and Smell Clinic, Department of Otorhinolaryngology, Hospital Clinic Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, University of Barcelona, Barcelona
7Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany
8Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals Research and Development (R&D), AstraZeneca, Durham, NC
9Biometrics, Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD
10Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
11Patient-Centered Science, Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD
12Global Clinical Development–Medical, Amgen, Thousand Oaks, CA
13Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD
14Early-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom
15Biometrics, Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
16Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom
Notes
Dr. Han can be contacted at [emailprotected] or at the Department of Otolaryngology, Head and Neck Surgery, 600 Gresham Dr., Ste. 1100, Eastern Virginia Medical School, Norfolk, VA 23507.
*
A complete list of the WAYPOINT study investigators is provided in the Supplementary Appendix, available at NEJM.org.
Drs. Lipworth and Han contributed equally to this article.
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