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Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS)
BACKGROUND: Lebrikizumab is a monoclonal antibody that modulates activity of interleukin‐13. The Phase 3 ACOUSTICS study assessed lebrikizumab efficacy and safety in adolescents with uncontrolled asthma despite standard‐of‐care treatment. METHODS: Adolescents (aged 12–17 years) with uncontrolled ast...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281483/ https://www.ncbi.nlm.nih.gov/pubmed/35846226 http://dx.doi.org/10.1002/clt2.12176 |
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author | Szefler, Stanley J. Roberts, Graham Rubin, Adalberto S. Zielen, Stefan Kuna, Piotr Alpan, Oral Anzures‐Cabrera, Judith Chen, Qiang Holweg, Cécile T. J. Kaminski, Janusz Putnam, Wendy S. Matthews, John G. Kamath, Nikhil |
author_facet | Szefler, Stanley J. Roberts, Graham Rubin, Adalberto S. Zielen, Stefan Kuna, Piotr Alpan, Oral Anzures‐Cabrera, Judith Chen, Qiang Holweg, Cécile T. J. Kaminski, Janusz Putnam, Wendy S. Matthews, John G. Kamath, Nikhil |
author_sort | Szefler, Stanley J. |
collection | PubMed |
description | BACKGROUND: Lebrikizumab is a monoclonal antibody that modulates activity of interleukin‐13. The Phase 3 ACOUSTICS study assessed lebrikizumab efficacy and safety in adolescents with uncontrolled asthma despite standard‐of‐care treatment. METHODS: Adolescents (aged 12–17 years) with uncontrolled asthma, prebronchodilator forced expiratory volume in 1 s 40%–90% predicted, and stable background therapy were randomised 1:1:1 to receive lebrikizumab 125 or 37.5 mg or placebo subcutaneously once every 4 weeks. Primary efficacy endpoint was asthma exacerbation rate over 52 weeks. RESULTS: Between August 2013 and July 2016, 579 patients were screened and 346 were randomised; 224 (65%) completed the study with 52 weeks of treatment. Lebrikizumab 125 mg (n = 116) reduced the exacerbation rate at 52 weeks versus placebo (n = 117; adjusted rate ratio [RR] 0.49 [95% CI 0.28–0.83]; 51% rate reduction). Lebrikizumab 37.5 mg (n = 113) was less effective at reducing exacerbations (RR 0.60 [95% CI 0.35–1.03]; 40% rate reduction). In patients with blood eosinophil counts ≥300 cells/μl, both lebrikizumab doses reduced exacerbations (125 mg: RR 0.44 [95% CI 0.21–0.89]; 37.5 mg: 0.42 [95% CI 0.19–0.93]). Treatment‐emergent adverse events, serious adverse events, and adverse events leading to study discontinuation occurred in 155 (68%), 7 (3%), and 5 (2%) of 229 patients who received lebrikizumab (both 125 and 37.5 mg doses) and in 72 (62%), 4 (3%), and 1 (1%) of 117 who received placebo, respectively. No deaths occurred. CONCLUSION: Lebrikizumab 125 mg reduced asthma exacerbation rates in adolescents with uncontrolled asthma. However, the study was prematurely terminated (sponsor's decision) potentially limiting interpretation of results. CLINICAL TRIAL REGISTRATION: NCT01875003 (www.ClinicalTrials.gov). |
format | Online Article Text |
id | pubmed-9281483 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92814832022-07-15 Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS) Szefler, Stanley J. Roberts, Graham Rubin, Adalberto S. Zielen, Stefan Kuna, Piotr Alpan, Oral Anzures‐Cabrera, Judith Chen, Qiang Holweg, Cécile T. J. Kaminski, Janusz Putnam, Wendy S. Matthews, John G. Kamath, Nikhil Clin Transl Allergy Original Article BACKGROUND: Lebrikizumab is a monoclonal antibody that modulates activity of interleukin‐13. The Phase 3 ACOUSTICS study assessed lebrikizumab efficacy and safety in adolescents with uncontrolled asthma despite standard‐of‐care treatment. METHODS: Adolescents (aged 12–17 years) with uncontrolled asthma, prebronchodilator forced expiratory volume in 1 s 40%–90% predicted, and stable background therapy were randomised 1:1:1 to receive lebrikizumab 125 or 37.5 mg or placebo subcutaneously once every 4 weeks. Primary efficacy endpoint was asthma exacerbation rate over 52 weeks. RESULTS: Between August 2013 and July 2016, 579 patients were screened and 346 were randomised; 224 (65%) completed the study with 52 weeks of treatment. Lebrikizumab 125 mg (n = 116) reduced the exacerbation rate at 52 weeks versus placebo (n = 117; adjusted rate ratio [RR] 0.49 [95% CI 0.28–0.83]; 51% rate reduction). Lebrikizumab 37.5 mg (n = 113) was less effective at reducing exacerbations (RR 0.60 [95% CI 0.35–1.03]; 40% rate reduction). In patients with blood eosinophil counts ≥300 cells/μl, both lebrikizumab doses reduced exacerbations (125 mg: RR 0.44 [95% CI 0.21–0.89]; 37.5 mg: 0.42 [95% CI 0.19–0.93]). Treatment‐emergent adverse events, serious adverse events, and adverse events leading to study discontinuation occurred in 155 (68%), 7 (3%), and 5 (2%) of 229 patients who received lebrikizumab (both 125 and 37.5 mg doses) and in 72 (62%), 4 (3%), and 1 (1%) of 117 who received placebo, respectively. No deaths occurred. CONCLUSION: Lebrikizumab 125 mg reduced asthma exacerbation rates in adolescents with uncontrolled asthma. However, the study was prematurely terminated (sponsor's decision) potentially limiting interpretation of results. CLINICAL TRIAL REGISTRATION: NCT01875003 (www.ClinicalTrials.gov). John Wiley and Sons Inc. 2022-07-14 /pmc/articles/PMC9281483/ /pubmed/35846226 http://dx.doi.org/10.1002/clt2.12176 Text en © 2022 The Authors. Clinical and Translational Allergy published by John Wiley and Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Szefler, Stanley J. Roberts, Graham Rubin, Adalberto S. Zielen, Stefan Kuna, Piotr Alpan, Oral Anzures‐Cabrera, Judith Chen, Qiang Holweg, Cécile T. J. Kaminski, Janusz Putnam, Wendy S. Matthews, John G. Kamath, Nikhil Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS) |
title | Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS) |
title_full | Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS) |
title_fullStr | Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS) |
title_full_unstemmed | Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS) |
title_short | Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS) |
title_sort | efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (acoustics) |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281483/ https://www.ncbi.nlm.nih.gov/pubmed/35846226 http://dx.doi.org/10.1002/clt2.12176 |
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