ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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Effect of Tezepelumab in Oral Corticosteroid-Dependent Patients with Severe Asthma: Results From the Phase 3 NAVIGATOR Study
Session Title
TP10 - TP010 CLINICAL AND POPULATION-LEVEL STUDIES OF ASTHMA
Abstract
A1442 - Effect of Tezepelumab in Oral Corticosteroid-Dependent Patients with Severe Asthma: Results From the Phase 3 NAVIGATOR Study
Author Block: A. Menzies-Gow1, C. E. Brightling2, C. S. Ambrose3, B. Cook3, Å. Hellqvist4, J. Llanos Ackert5, G. Colice6, M. Wechsler7; 1Royal Brompton Hospital, London, United Kingdom, 2NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, United Kingdom, 3Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, United States, 4Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 5Global Medical Affairs, Amgen, Thousand Oaks, CA, United States, 6Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States, 7National Jewish Health, Denver, CO, United States.
RATIONALE
Chronic (≥6 months) daily maintenance oral corticosteroid (mOCS) use is prevalent in patients with severe asthma and is associated with significant adverse effects. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial-derived cytokine implicated in asthma pathogenesis. In the phase 2b PATHWAY study (NCT02054130), tezepelumab treatment (210 mg every 4 weeks [Q4W]) reduced asthma exacerbations by 75% (95% confidence interval [CI]: 11, 93) in the subgroup of patients with severe, uncontrolled asthma receiving mOCS (n=23). The phase 3 NAVIGATOR study (NCT03347279) evaluated the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in patients from NAVIGATOR who were receiving mOCS at baseline and throughout the study.
METHODS
NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12-80 years old) receiving medium- or high-dose inhaled corticosteroids with ≥1 additional controller medication with or without mOCS were randomized 1:1 to receive tezepelumab 210 mg subcutaneously or placebo Q4W for 52 weeks. The annualized asthma exacerbation rate (AAER) over 52 weeks was estimated in the two treatment groups using a negative binomial regression model. The least-squares (LS) mean change from baseline to week 52 and the LS mean difference versus placebo were estimated for the key secondary endpoints of pre-bronchodilator forced expiratory volume in 1 second (FEV1), and Asthma Control Questionnaire-6 (ACQ-6), Asthma Quality of Life Questionnaire (AQLQ) and Asthma Symptom Diary (ASD) scores, using a mixed model for repeated measures. To obtain estimates for the mOCS subgroup, mOCS use and treatment-by-mOCS interaction were included as covariates in the models.
RESULTS
Of 1061 randomized patients, 100 were receiving mOCS (tezepelumab, n=49; placebo, n=51). In the mOCS subgroup, tezepelumab-treated patients had a numerically lower AAER than placebo-treated patients (2.12 vs 2.94; 28% [95% CI: −26, 59] reduction). Compared with placebo, tezepelumab improved pre-bronchodilator FEV1 (LS mean difference [95% CI]: 270 mL [100, 440]) and ACQ-6 (LS mean difference [95% CI]: −0.65 [−1.08, −0.22]), AQLQ (LS mean difference [95% CI]: 0.50 [0.04, 0.97]) and ASD (LS mean difference [95% CI]: −0.29 [−0.56, −0.03]) scores (Table).
CONCLUSIONS
In adults and adolescents with severe, uncontrolled asthma requiring mOCS, additional treatment with tezepelumab resulted in a numerically lower rate of exacerbations, and clinically meaningful improvements in lung function, quality of life and asthma symptoms versus placebo. These findings support the benefits of tezepelumab in patients with severe, OCS-dependent asthma.
Author Block: A. Menzies-Gow1, C. E. Brightling2, C. S. Ambrose3, B. Cook3, Å. Hellqvist4, J. Llanos Ackert5, G. Colice6, M. Wechsler7; 1Royal Brompton Hospital, London, United Kingdom, 2NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, United Kingdom, 3Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, United States, 4Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 5Global Medical Affairs, Amgen, Thousand Oaks, CA, United States, 6Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States, 7National Jewish Health, Denver, CO, United States.
RATIONALE
Chronic (≥6 months) daily maintenance oral corticosteroid (mOCS) use is prevalent in patients with severe asthma and is associated with significant adverse effects. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial-derived cytokine implicated in asthma pathogenesis. In the phase 2b PATHWAY study (NCT02054130), tezepelumab treatment (210 mg every 4 weeks [Q4W]) reduced asthma exacerbations by 75% (95% confidence interval [CI]: 11, 93) in the subgroup of patients with severe, uncontrolled asthma receiving mOCS (n=23). The phase 3 NAVIGATOR study (NCT03347279) evaluated the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in patients from NAVIGATOR who were receiving mOCS at baseline and throughout the study.
METHODS
NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12-80 years old) receiving medium- or high-dose inhaled corticosteroids with ≥1 additional controller medication with or without mOCS were randomized 1:1 to receive tezepelumab 210 mg subcutaneously or placebo Q4W for 52 weeks. The annualized asthma exacerbation rate (AAER) over 52 weeks was estimated in the two treatment groups using a negative binomial regression model. The least-squares (LS) mean change from baseline to week 52 and the LS mean difference versus placebo were estimated for the key secondary endpoints of pre-bronchodilator forced expiratory volume in 1 second (FEV1), and Asthma Control Questionnaire-6 (ACQ-6), Asthma Quality of Life Questionnaire (AQLQ) and Asthma Symptom Diary (ASD) scores, using a mixed model for repeated measures. To obtain estimates for the mOCS subgroup, mOCS use and treatment-by-mOCS interaction were included as covariates in the models.
RESULTS
Of 1061 randomized patients, 100 were receiving mOCS (tezepelumab, n=49; placebo, n=51). In the mOCS subgroup, tezepelumab-treated patients had a numerically lower AAER than placebo-treated patients (2.12 vs 2.94; 28% [95% CI: −26, 59] reduction). Compared with placebo, tezepelumab improved pre-bronchodilator FEV1 (LS mean difference [95% CI]: 270 mL [100, 440]) and ACQ-6 (LS mean difference [95% CI]: −0.65 [−1.08, −0.22]), AQLQ (LS mean difference [95% CI]: 0.50 [0.04, 0.97]) and ASD (LS mean difference [95% CI]: −0.29 [−0.56, −0.03]) scores (Table).
CONCLUSIONS
In adults and adolescents with severe, uncontrolled asthma requiring mOCS, additional treatment with tezepelumab resulted in a numerically lower rate of exacerbations, and clinically meaningful improvements in lung function, quality of life and asthma symptoms versus placebo. These findings support the benefits of tezepelumab in patients with severe, OCS-dependent asthma.
