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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Reductions in Inflammatory Biomarkers in Patients with Oral Corticosteroid-Dependent Asthma Treated with Tezepelumab
Session Title
TP10 - TP010 CLINICAL AND POPULATION-LEVEL STUDIES OF ASTHMA
Abstract
A1454 - Reductions in Inflammatory Biomarkers in Patients with Oral Corticosteroid-Dependent Asthma Treated with Tezepelumab
Author Block: M. Wechsler1, A. Menzies Gow2, C. E. Brightling3, P. Kuna4, S. Korn5, T. Welte6, J. M. Griffiths7, K. Sałapa8, Å. Hellqvist9, G. Almqvist10, P. Kaur11, T. Skärby10, G. Colice12; 1National Jewish Health, Denver, CO, United States, 2Royal Brompton Hospital, London, United Kingdom, 3NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, United Kingdom, 4Department of Internal Medicine, Asthma and Allergy, Medical University of Łódź, Łódź, Poland, 5Pulmonary Department, Mainz University Hospital, Mainz, Germany, 6Department of Respiratory Medicine and German Center for Lung Research, Hannover Medical School, Hannover, Germany, 7Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, AstraZeneca, Gaithersburg, MD, United States, 8Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Warsaw, Poland, 9Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 10Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 11Global Development, Amgen, Thousand Oaks, CA, United States, 12Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
RATIONALE
Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine implicated in asthma pathogenesis. The phase 3 SOURCE study (NCT03406078) evaluated the oral corticosteroid (OCS)-sparing effects of tezepelumab in adults with OCS-dependent asthma. One of the secondary objectives of SOURCE was to evaluate the effect of tezepelumab on inflammatory biomarkers.
METHODS
SOURCE was a multicenter, randomized, double-blind, placebo-controlled study. After an OCS optimization period of up to 8 weeks, patients (18-80 years old) with OCS-dependent asthma were randomized 1:1 to receive tezepelumab 210 mg subcutaneously or placebo every 4 weeks for 48 weeks (comprising a 4-week induction phase, a 36-week OCS reduction phase and an 8-week maintenance phase). Blood eosinophil counts and levels of fractional exhaled nitric oxide (FeNO) and serum total immunoglobulin (Ig) E were measured at baseline and at weeks 4, 12, 24, 40 and 48 of treatment. Changes from baseline to week 48 in these biomarkers were analyzed in the tezepelumab and placebo groups using a mixed model for repeated measures.
RESULTS
Overall, 150 patients were randomized (tezepelumab 210 mg, n = 74; placebo, n = 76). Reductions from baseline to week 48 were greater in the tezepelumab group than in the placebo group for blood eosinophil count (least-squares [LS] mean difference [95% CI]: −117.2 cells/µL [−164.4, −70.0]), FeNO (LS mean difference [95% CI]: −10.3 ppb [−18.1, −2.6]) and serum total IgE (LS mean difference [95% CI]: −118.4 IU/mL [−219.3, −17.6]) (Table). Reductions in blood eosinophil counts and FeNO in the tezepelumab group were observed as early as the first post-baseline measurement time point (week 4) and were sustained throughout the treatment period. Serum total IgE decreased from baseline to week 48.
CONCLUSIONS
Treatment with tezepelumab reduced blood eosinophil counts, FeNO and serum total IgE compared with placebo in patients with OCS-dependent asthma, despite reductions in maintenance OCS dose. Reductions in these biomarkers were consistent with observations made in other clinical studies of tezepelumab and demonstrate that tezepelumab may have an effect on multiple inflammatory pathways.
Author Block: M. Wechsler1, A. Menzies Gow2, C. E. Brightling3, P. Kuna4, S. Korn5, T. Welte6, J. M. Griffiths7, K. Sałapa8, Å. Hellqvist9, G. Almqvist10, P. Kaur11, T. Skärby10, G. Colice12; 1National Jewish Health, Denver, CO, United States, 2Royal Brompton Hospital, London, United Kingdom, 3NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, United Kingdom, 4Department of Internal Medicine, Asthma and Allergy, Medical University of Łódź, Łódź, Poland, 5Pulmonary Department, Mainz University Hospital, Mainz, Germany, 6Department of Respiratory Medicine and German Center for Lung Research, Hannover Medical School, Hannover, Germany, 7Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, AstraZeneca, Gaithersburg, MD, United States, 8Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Warsaw, Poland, 9Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 10Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 11Global Development, Amgen, Thousand Oaks, CA, United States, 12Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
RATIONALE
Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine implicated in asthma pathogenesis. The phase 3 SOURCE study (NCT03406078) evaluated the oral corticosteroid (OCS)-sparing effects of tezepelumab in adults with OCS-dependent asthma. One of the secondary objectives of SOURCE was to evaluate the effect of tezepelumab on inflammatory biomarkers.
METHODS
SOURCE was a multicenter, randomized, double-blind, placebo-controlled study. After an OCS optimization period of up to 8 weeks, patients (18-80 years old) with OCS-dependent asthma were randomized 1:1 to receive tezepelumab 210 mg subcutaneously or placebo every 4 weeks for 48 weeks (comprising a 4-week induction phase, a 36-week OCS reduction phase and an 8-week maintenance phase). Blood eosinophil counts and levels of fractional exhaled nitric oxide (FeNO) and serum total immunoglobulin (Ig) E were measured at baseline and at weeks 4, 12, 24, 40 and 48 of treatment. Changes from baseline to week 48 in these biomarkers were analyzed in the tezepelumab and placebo groups using a mixed model for repeated measures.
RESULTS
Overall, 150 patients were randomized (tezepelumab 210 mg, n = 74; placebo, n = 76). Reductions from baseline to week 48 were greater in the tezepelumab group than in the placebo group for blood eosinophil count (least-squares [LS] mean difference [95% CI]: −117.2 cells/µL [−164.4, −70.0]), FeNO (LS mean difference [95% CI]: −10.3 ppb [−18.1, −2.6]) and serum total IgE (LS mean difference [95% CI]: −118.4 IU/mL [−219.3, −17.6]) (Table). Reductions in blood eosinophil counts and FeNO in the tezepelumab group were observed as early as the first post-baseline measurement time point (week 4) and were sustained throughout the treatment period. Serum total IgE decreased from baseline to week 48.
CONCLUSIONS
Treatment with tezepelumab reduced blood eosinophil counts, FeNO and serum total IgE compared with placebo in patients with OCS-dependent asthma, despite reductions in maintenance OCS dose. Reductions in these biomarkers were consistent with observations made in other clinical studies of tezepelumab and demonstrate that tezepelumab may have an effect on multiple inflammatory pathways.
