Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS)
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 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).
IL-13, adolescents, lebrikizumab, uncontrolled asthma
e12176
Szefler, Stanley J
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Roberts, Graham
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Rubin, Adalberto S
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Zielen, Stefan
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Kuna, Piotr
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Alpan, Oral
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Anzures-Cabrera, Judith
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Chen, Qiang
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Holweg, Cécile T J
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Kaminski, Janusz
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Putnam, Wendy S
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Matthews, John G
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Kamath, Nikhil
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1 July 2022
Szefler, Stanley J
fe2da620-7a3c-4bef-9450-303925b19c8f
Roberts, Graham
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Rubin, Adalberto S
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Zielen, Stefan
660c9e21-1eb7-45f6-b4be-7df45fcd77af
Kuna, Piotr
0982046a-9893-4920-842d-49f032302edc
Alpan, Oral
ca4ee1e9-d02a-4ec1-bd07-5b91637cd442
Anzures-Cabrera, Judith
891f5546-4425-450a-99d1-07c8f0d7b2bf
Chen, Qiang
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Holweg, Cécile T J
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Kaminski, Janusz
aa5d01ff-2f09-496d-a68f-b6afa8759e8c
Putnam, Wendy S
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Matthews, John G
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Kamath, Nikhil
bbddc210-ea40-4a37-a6dc-85351c8a3852
Szefler, Stanley J, Roberts, Graham and Rubin, Adalberto S
,
et al.
(2022)
Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS).
Clinical and Translational Allergy, 12 (7), , [e12176].
(doi:10.1002/clt2.12176).
Abstract
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).
Text
Efficacy_safety_ and_tolerability_of_lebrikizumab
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Accepted/In Press date: 21 June 2022
Published date: 1 July 2022
Additional Information:
Funding Information:
This research was funded by F. Hoffmann-La Roche Ltd. Financial support for third-party writing assistance of this manuscript, furnished by Aeric Deutsch, PhD, CMPP, and Benjamin L Ricca, PhD, of Health Interactions, Inc, was provided by F. Hoffmann-La Roche Ltd. and Dermira, Inc.
Funding Information:
This research was funded by F. Hoffmann‐La Roche Ltd. Financial support for third‐party writing assistance of this manuscript, furnished by Aeric Deutsch, PhD, CMPP, and Benjamin L Ricca, PhD, of Health Interactions, Inc, was provided by F. Hoffmann‐La Roche Ltd. and Dermira, Inc.
Publisher Copyright:
© 2022 The Authors. Clinical and Translational Allergy published by John Wiley and Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.
Keywords:
IL-13, adolescents, lebrikizumab, uncontrolled asthma
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Local EPrints ID: 476988
URI: http://eprints.soton.ac.uk/id/eprint/476988
ISSN: 2045-7022
PURE UUID: f8cb550c-9f92-46ba-bcb3-296e6b649fdf
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Date deposited: 23 May 2023 16:33
Last modified: 17 Mar 2024 03:02
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Author:
Stanley J Szefler
Author:
Adalberto S Rubin
Author:
Stefan Zielen
Author:
Piotr Kuna
Author:
Oral Alpan
Author:
Judith Anzures-Cabrera
Author:
Qiang Chen
Author:
Cécile T J Holweg
Author:
Janusz Kaminski
Author:
Wendy S Putnam
Author:
John G Matthews
Author:
Nikhil Kamath
Corporate Author: et al.
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