Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS). Issue 7 (14th July 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Clinical and translational allergy. Volume 12:Issue 7(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-07-14
• Subjects: adolescents -- IL‐13 -- lebrikizumab -- uncontrolled asthma; Allergy -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Hypersensitivity -- Periodicals; Immune System Phenomena -- Periodicals; 616.97005
• DOI: 10.1002/clt2.12176
• Languages: English
• ISSNs: 2045-7022

Abstract

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 ).