Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma.


Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
13 05 2021
Historique:
entrez: 12 5 2021
pubmed: 13 5 2021
medline: 19 5 2021
Statut: ppublish

Résumé

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell-derived cytokine implicated in the pathogenesis of asthma. The efficacy and safety of tezepelumab in patients with severe, uncontrolled asthma require further assessment. We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients (12 to 80 years of age) were randomly assigned to receive tezepelumab (210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. The primary end point was the annualized rate of asthma exacerbations over a period of 52 weeks. This end point was also assessed in patients with baseline blood eosinophil counts of less than 300 cells per microliter. Secondary end points included the forced expiratory volume in 1 second (FEV Overall, 1061 patients underwent randomization (529 were assigned to receive tezepelumab and 532 to receive placebo). The annualized rate of asthma exacerbations was 0.93 (95% confidence interval [CI], 0.80 to 1.07) with tezepelumab and 2.10 (95% CI, 1.84 to 2.39) with placebo (rate ratio, 0.44; 95% CI, 0.37 to 0.53; P<0.001). In patients with a blood eosinophil count of less than 300 cells per microliter, the annualized rate was 1.02 (95% CI, 0.84 to 1.23) with tezepelumab and 1.73 (95% CI, 1.46 to 2.05) with placebo (rate ratio, 0.59; 95% CI, 0.46 to 0.75; P<0.001). At week 52, improvements were greater with tezepelumab than with placebo with respect to the prebronchodilator FEV Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo. (Funded by AstraZeneca and Amgen; NAVIGATOR ClinicalTrials.gov number, NCT03347279.).

Sections du résumé

BACKGROUND
Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell-derived cytokine implicated in the pathogenesis of asthma. The efficacy and safety of tezepelumab in patients with severe, uncontrolled asthma require further assessment.
METHODS
We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients (12 to 80 years of age) were randomly assigned to receive tezepelumab (210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. The primary end point was the annualized rate of asthma exacerbations over a period of 52 weeks. This end point was also assessed in patients with baseline blood eosinophil counts of less than 300 cells per microliter. Secondary end points included the forced expiratory volume in 1 second (FEV
RESULTS
Overall, 1061 patients underwent randomization (529 were assigned to receive tezepelumab and 532 to receive placebo). The annualized rate of asthma exacerbations was 0.93 (95% confidence interval [CI], 0.80 to 1.07) with tezepelumab and 2.10 (95% CI, 1.84 to 2.39) with placebo (rate ratio, 0.44; 95% CI, 0.37 to 0.53; P<0.001). In patients with a blood eosinophil count of less than 300 cells per microliter, the annualized rate was 1.02 (95% CI, 0.84 to 1.23) with tezepelumab and 1.73 (95% CI, 1.46 to 2.05) with placebo (rate ratio, 0.59; 95% CI, 0.46 to 0.75; P<0.001). At week 52, improvements were greater with tezepelumab than with placebo with respect to the prebronchodilator FEV
CONCLUSIONS
Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo. (Funded by AstraZeneca and Amgen; NAVIGATOR ClinicalTrials.gov number, NCT03347279.).

Identifiants

pubmed: 33979488
doi: 10.1056/NEJMoa2034975
doi:

Substances chimiques

Anti-Asthmatic Agents 0
Antibodies, Monoclonal, Humanized 0
tezepelumab RJ1IW3B4QX

Banques de données

ClinicalTrials.gov
['NCT03347279']

Types de publication

Clinical Trial, Phase III Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1800-1809

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 Massachusetts Medical Society.

Auteurs

Andrew Menzies-Gow (A)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Jonathan Corren (J)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Arnaud Bourdin (A)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Geoffrey Chupp (G)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Elliot Israel (E)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Michael E Wechsler (ME)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Christopher E Brightling (CE)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Janet M Griffiths (JM)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Åsa Hellqvist (Å)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Karin Bowen (K)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Primal Kaur (P)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Gun Almqvist (G)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Sandhia Ponnarambil (S)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Gene Colice (G)

From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) - all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) - both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

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