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; Joseph K Han; Jason K Lee; Tanya M Laidlaw; Nicole L Martin; Scott Caveney; Christopher S Ambrose; Neil Martin; Joseph D Spahn; Flavia C L Hoyte

doi:10.1007/s12325-024-03006-5

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

Adv Ther. 2024 Nov 8. doi: 10.1007/s12325-024-03006-5. Online ahead of print.

Authors

Joshua S Jacobs¹, Joseph K Han², Jason K Lee^{3

4}, Tanya M Laidlaw⁵, Nicole L Martin^{6

7

8}, Scott Caveney⁹, Christopher S Ambrose¹⁰, Neil Martin¹¹, Joseph D Spahn¹², Flavia C L Hoyte¹³

Affiliations

¹ Allergy and Asthma Clinical Research, 370 North Widget Lane, Suite 210, Walnut Creek, CA, 94598, USA. jjacobs@bayareaallergy.com.
² Department of Otolaryngology & Head & Neck Surgery, Eastern Virginia Medical School, Norfolk, VA, USA.
³ Evidence Based Medical Educator Inc., Toronto, ON, Canada.
⁴ Toronto Allergy and Asthma Clinic, Toronto, ON, Canada.
⁵ Division of Allergy and Clinical Immunology, Department of Medicine, Jeff and Penny Vinik Center for Translational Immunology Research, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Biometrics, Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Waltham, MA, USA.
⁷ Cytel Inc., Waltham, MA, USA.
⁸ Global Development, Inflammation, R&D, Amgen, Thousand Oaks, CA, USA.
⁹ Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA.
¹⁰ Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK.
¹¹ Institute for Lung Health, National Institute for Health and Care Research, Leicester Biomedical Research Centre, University of Leicester, Leicester, UK.
¹² Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Wilmington, DE, USA.
¹³ Division of Allergy and Immunology, National Jewish Health, Denver, CO, USA.

PMID: 39514041
DOI: 10.1007/s12325-024-03006-5

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.

Associated data

ClinicalTrials.gov/NCT03347279