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Randomized Controlled Trial
. 2025 Jan;42(1):510-522.
doi: 10.1007/s12325-024-03006-5. Epub 2024 Nov 8.

Effect of Tezepelumab on Sino-Nasal Outcome Test (SNOT)-22 Domain and Symptom-Specific Scores in Patients with Severe, Uncontrolled Asthma and a History of Chronic Rhinosinusitis with Nasal Polyps

Joshua S Jacobs  1 , Joseph K Han  2 , Jason K Lee  3   4 , Tanya M Laidlaw  5 , Nicole L Martin  6   7   8 , Scott Caveney  9 , Christopher S Ambrose  10 , Neil Martin  11 , Joseph D Spahn  12 , Flavia C L Hoyte  13
Affiliations
Randomized Controlled Trial

Effect of Tezepelumab on Sino-Nasal Outcome Test (SNOT)-22 Domain and Symptom-Specific Scores in Patients with Severe, Uncontrolled Asthma and a History of Chronic Rhinosinusitis with Nasal Polyps

Joshua S Jacobs et al. Adv Ther. 2025 Jan.

Abstract

Introduction: Tezepelumab blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine implicated in the pathogenesis of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In a previous analysis, tezepelumab improved asthma and rhinosinusitis symptoms compared with placebo in patients with severe, uncontrolled asthma and a history of CRSwNP in the 2 years before randomization in the NAVIGATOR study. This post hoc analysis of patients with a CRSwNP diagnosis at any time before randomization in NAVIGATOR enabled domain and symptom-specific analyses of Sino-Nasal Outcome Test (SNOT)-22 outcomes.

Methods: Patients (aged 12-80 years) with severe, uncontrolled asthma were randomized to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. SNOT-22 total, domain, and item scores were assessed in patients with a history of CRSwNP. Annualized asthma exacerbation rate (primary efficacy outcome), pre-bronchodilator forced expiratory volume in 1 s, and Asthma Control Questionnaire-6, Asthma Quality of Life Questionnaire (standardized) for patients 12 years and older, and Asthma Symptom Diary scores were also assessed in patients with and without a history of CRSwNP.

Results: Of 1059 patients with severe asthma, 165 (15.6%) had a history of CRSwNP. Tezepelumab treatment resulted in sustained improvements versus placebo in SNOT-22 total score throughout the 52-week study period [least-squares mean difference (95% confidence interval) - 11.08 (- 17.80, - 4.35)]. Tezepelumab improved all five SNOT-22 domain scores (sleep, nasal, function, ear/facial, and emotion) and the five SNOT-22 item scores of most clinical interest (decreased sense of smell/taste, nasal blockage, reduced productivity, waking up tired, and cough). Tezepelumab improved asthma-related clinical outcomes in patients with and without a history of CRSwNP.

Conclusion: In patients with severe, uncontrolled asthma and a history of CRSwNP, tezepelumab improved rhinosinusitis symptoms across multiple domains, as well as asthma exacerbations, lung function, asthma control, and health-related quality of life.

Gov identifier: NCT03347279 ( https://classic.

Clinicaltrials: gov/ct2/show/NCT03347279 ).

Keywords: Asthma; Biologic; Chronic rhinosinusitis; Nasal polyps; Sino-Nasal Outcome Test-22; Tezepelumab; Thymic stromal lymphopoietin.

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Conflict of interest statement

Declarations. Conflict of Interest: Joshua S. Jacobs has received fees for sponsored research, consultancy and speaking from AstraZeneca, Genentech, GSK, Regeneron Pharmaceuticals, and Teva Pharmaceuticals; Joseph K. Han has received consultancy fees from AstraZeneca, Genentech, Gossamer Bio, Novartis, Regeneron Pharmaceuticals, and Sanofi; Jason K. Lee has received research support from AstraZeneca, Genentech, GSK, Medexus, Novartis, Regeneron Pharmaceuticals, Roche, Sanofi, and Takeda; has received fees for speakers bureau from Aralez Bio, AstraZeneca, GSK, Medexus, Merck, Mylan, Novartis, and Sanofi; and receives consultancy fees from and is an advisory committee member of AstraZeneca, GSK, Medexus, Novartis, Regeneron Pharmaceuticals, and Sanofi; Tanya M. Laidlaw has served on scientific advisory boards for Eli Lilly, GSK, Regeneron Pharmaceuticals, and Sanofi; Nicole L. Martin, Christopher S. Ambrose, Neil Martin, and Joseph D. Spahn are employees of AstraZeneca and may own stock or stock options in AstraZeneca; Scott Caveney is an employee of Amgen and owns stock in Amgen; Flavia C. L. Hoyte has received honoraria from AstraZeneca, Genentech, Sanofi and Teva Pharmaceuticals; has participated in research with Genentech and Sanofi, for which her institution has been remunerated; and her family owns stock in Amgen. Ethical Approval: The study was conducted in accordance with the ethical principles of the Declaration of Helsinki, International Council for Harmonisation Good Clinical Practice guidelines and applicable regulatory requirements. Approvals were obtained from the Copernicus Central Institutional Review Board (Cary, NC, USA), and local independent ethics committees. All patients or their guardians provided written informed consent in accordance with local requirements.

Figures

Fig. 1
Fig. 1
a–g Changes from baseline in SNOT-22 total and domain scores in patients with a history of CRSwNP in the NAVIGATOR study. n is the number of patients with a change from baseline value at each time point. The dotted line represents no treatment difference. CI confidence interval, CRSwNP chronic rhinosinusitis with nasal polyps, LS least-squares, Q4W every 4 weeks, SD standard deviation, SE standard error, SNOT-22 Sino-Nasal Outcome Test-22
Fig. 2
Fig. 2
a–e Changes from baseline to week 52 in the five SNOT-22 item scores of most clinical interest in patients with a history of CRSwNP in the NAVIGATOR study. n is the number of patients contributing to the analysis, i.e., the number of patients with a baseline value and no missing independent variables included in the model. CI confidence interval, CRSwNP chronic rhinosinusitis with nasal polyps, LS least-squares, Q4W every 4 weeks, SE standard error, SNOT-22 Sino-Nasal Outcome Test-22
See this image and copyright information in PMC

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