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
Department of Pediatrics Children's Hospital Colorado and the University of Colorado School of Medicine Anschutz Medical Campus Aurora Colorado USA.
University of Southampton School of Medicine and Southampton Biomedical Research Centre University Hospital Southampton NHS Foundation Trust Southampton UK.
Clin Transl Allergy. 2022 Jul 14;12(7):e12176. doi: 10.1002/clt2.12176. eCollection 2022 Jul.
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.
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.
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 ( = 116) reduced the exacerbation rate at 52 weeks versus placebo ( = 117; adjusted rate ratio [RR] 0.49 [95% CI 0.28-0.83]; 51% rate reduction). Lebrikizumab 37.5 mg ( = 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.
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.
NCT01875003 (www.ClinicalTrials.gov).
瑞莎珠单抗是一种调节白细胞介素-13活性的单克隆抗体。3期ACOUSTICS研究评估了瑞莎珠单抗在接受标准治疗后哮喘仍未得到控制的青少年中的疗效和安全性。
哮喘未得到控制、支气管扩张剂使用前1秒用力呼气量占预计值40%-90%且背景治疗稳定的青少年（12-17岁）按1:1:1随机分组，每4周皮下注射一次125毫克或37.5毫克瑞莎珠单抗或安慰剂。主要疗效终点是52周内的哮喘加重率。
2013年8月至2016年7月，579例患者接受筛查，346例患者被随机分组；224例（65%）完成了52周的治疗。与安慰剂组（n = 117）相比，125毫克瑞莎珠单抗组（n = 116）在52周时降低了加重率（校正率比[RR] 0.49 [95% CI 0.28 - 0.83]；降低率51%）。37.5毫克瑞莎珠单抗组（n = 113）在降低加重率方面效果较差（RR 0.60 [95% CI 0.35 - 1.03]；降低率40%）。在血液嗜酸性粒细胞计数≥300个/μl的患者中，两种剂量的瑞莎珠单抗均降低了加重率（125毫克：RR 0.44 [95% CI 0.21 - 0.89]；37.5毫克：0.42 [95% CI 0.19 - 0.93]）。在接受瑞莎珠单抗（125毫克和37.5毫克两种剂量）的229例患者中，155例（68%）发生了治疗中出现的不良事件、7例（3%）发生了严重不良事件、5例（2%）发生了导致研究停药的不良事件；在接受安慰剂的117例患者中，上述事件分别发生在72例（62%）、4例（3%）和1例（1%）。未发生死亡病例。
125毫克瑞莎珠单抗降低了哮喘未得到控制的青少年的哮喘加重率。然而，该研究被提前终止（申办方决定），这可能限制了对结果的解读。
NCT01875003（www.ClinicalTrials.gov）
