瑞莎珠单抗降低哮喘患者的2型炎症生物标志物水平：来自3期随机试验（LAVOLTA I和II）的数据
Lebrikizumab decreases type 2 inflammatory biomarker levels in patients with asthma: data from randomized phase 3 trials (LAVOLTA I and II).
作者信息
Szefler Stanley, Corren Jonathan, Silverberg Jonathan I, Okragly Angela, Sun Zhe, Natalie Chitra R, Zitnik Ralph, Siu Kimberly, Blauvelt Andrew
机构信息
The Breathing Institute and Pediatric Pulmonary and Sleep Medicine Section, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO, USA.
Division of Allergy and Clinical Immunology, Department of Medicine and Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
出版信息
Immunotherapy. 2024;16(20-22):1211-1216. doi: 10.1080/1750743X.2024.2439777. Epub 2025 Jan 9.
AIM
Lebrikizumab is an interleukin (IL)-13 inhibitor that specifically blocks IL-13 signaling. Here, we report the effects of lebrikizumab on asthma serum biomarkers in 2 phase 3 clinical studies.
METHODS
LAVOLTA I and LAVOLTA II are replicate, double-blind, placebo-controlled trials with 52-week placebo-controlled treatment periods that evaluated lebrikizumab 37.5- and 125-mg doses every 4 weeks. Patients were aged 18-75 years with uncontrolled asthma on stable background therapy. Biomarkers assessed included immunoglobulin E (IgE), periostin, CC motif chemokine ligand (CCL)13, and CCL17. Statistical significance was assessed for difference in fold-change for lebrikizumab versus placebo using a mixed-effects model for repeated measures.
RESULTS
At early time points in LAVOLTA I and II (weeks 1 and 4), decreases in periostin and CCL13 were statistically significant versus placebo (all < 0.001) for both lebrikizumab doses. For the 125-mg lebrikizumab dose at week 1 in LAVOLTA I, the decrease in CCL17 was statistically significant ( = 0.001). Reductions in periostin, CCL13, and CCL17 were maintained throughout the trial duration. Significant decreases versus placebo ( ≤ 0.001) were seen in IgE by weeks 12 and 24 in LAVOLTA I and LAVOLTA II, respectively.
CONCLUSION
Significant reductions in relevant inflammatory biomarkers were observed in the LAVOLTA I and LAVOLTA II studies.
目的
瑞莎珠单抗是一种白细胞介素（IL）-13抑制剂，可特异性阻断IL-13信号传导。在此，我们报告瑞莎珠单抗在两项3期临床研究中对哮喘血清生物标志物的影响。
方法
LAVOLTA I和LAVOLTA II是重复、双盲、安慰剂对照试验，有52周的安慰剂对照治疗期，评估每4周使用37.5毫克和125毫克剂量的瑞莎珠单抗。患者年龄在18至75岁之间，在稳定的背景治疗下哮喘未得到控制。评估的生物标志物包括免疫球蛋白E（IgE）、骨膜蛋白、CC基序趋化因子配体（CCL）13和CCL17。使用重复测量的混合效应模型评估瑞莎珠单抗与安慰剂的倍数变化差异的统计学显著性。
结果
在LAVOLTA I和II的早期时间点（第1周和第4周），两种瑞莎珠单抗剂量的骨膜蛋白和CCL13较安慰剂均有统计学显著下降（均<0.001）。在LAVOLTA I第1周时，125毫克瑞莎珠单抗剂量的CCL17下降具有统计学显著性（=0.001）。在整个试验期间，骨膜蛋白、CCL13和CCL17均持续下降。在LAVOLTA I和LAVOLTA II中，分别在第12周和第24周时，IgE较安慰剂有显著下降（≤0.001）。
结论
在LAVOLTA I和LAVOLTA II研究中观察到相关炎症生物标志物显著降低。
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