Lebrikizumab Treatment in Adults with Asthma
Lebrikizumab Treatment in Adults with Asthma
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DOI：
10.1056/nejmoa1106469
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发表时间：
2011-09-22
影响因子：
158.5
通讯作者：
Matthews, John G.
中科院分区：
文献类型：
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作者：
Corren, Jonathan;Lemanske, Robert F., Jr.;Matthews, John G.
背景
许多哮喘患者尽管接受了吸入性糖皮质激素治疗，但病情仍未得到控制。治疗反应存在差异的一个潜在原因是白细胞介素 - 13表达在临床哮喘表型中所起作用的异质性。我们假设抗白细胞介素 - 13疗法对那些治疗前特征符合白细胞介素 - 13活性的哮喘患者有益。
方法
我们对lebrikizumab（一种抗白细胞介素 - 13的单克隆抗体）进行了一项随机、双盲、安慰剂对照研究，研究对象为219名尽管接受了吸入性糖皮质激素治疗但哮喘仍控制不佳的成年人。主要疗效指标是从基线到第12周时，支气管扩张剂使用前1秒用力呼气量（FEV₁）的相对变化。次要疗效指标包括24周内哮喘加重的发生率。根据基线2型辅助性T细胞（Th2）状态（基于总IgE水平和血液嗜酸性粒细胞计数评估）以及血清骨膜蛋白水平预先设定了患者亚组。
结果
基线时，患者的平均FEV₁为预测值的65%，平均每日吸入性糖皮质激素剂量为580μg；80%的患者还使用了长效β - 激动剂。在第12周时，lebrikizumab组的FEV₁平均增加量比安慰剂组高5.5个百分点（P = 0.02）。在高骨膜蛋白亚组患者中，lebrikizumab组从基线FEV₁的增加量比安慰剂组高8.2个百分点（P = 0.03）。在低骨膜蛋白亚组患者中，lebrikizumab组从基线FEV₁的增加量比安慰剂组高1.6个百分点（P = 0.61）。lebrikizumab组的肌肉骨骼副作用比安慰剂组更常见（13.2%对5.4%，P = 0.045）。
结论
Lebrikizumab治疗与肺功能改善相关。治疗前血清骨膜蛋白水平高的患者使用lebrikizumab后肺功能改善程度比骨膜蛋白水平低的患者更大。（由基因泰克公司资助；ClinicalTrials.gov编号，NCT00930163）
BackgroundMany patients with asthma have uncontrolled disease despite treatment with inhaled glucocorticoids. One potential cause of the variability in response to treatment is heterogeneity in the role of interleukin-13 expression in the clinical asthma phenotype. We hypothesized that anti-interleukin-13 therapy would benefit patients with asthma who had a pretreatment profile consistent with interleukin-13 activity.MethodsWe conducted a randomized, double-blind, placebo-controlled study of lebrikizumab, a monoclonal antibody to interleukin-13, in 219 adults who had asthma that was inadequately controlled despite inhaled glucocorticoid therapy. The primary efficacy outcome was the relative change in prebronchodilator forced expiratory volume in 1 second (FEV(1)) from baseline to week 12. Among the secondary outcomes was the rate of asthma exacerbations through 24 weeks. Patient subgroups were prespecified according to baseline type 2 helper T-cell (Th2) status (assessed on the basis of total IgE level and blood eosinophil count) and serum periostin level.ResultsAt baseline, patients had a mean FEV(1) that was 65% of the predicted value and were taking a mean dose of inhaled glucocorticoids of 580 mu g per day; 80% were also taking a long-acting beta-agonist. At week 12, the mean increase in FEV(1) was 5.5 percentage points higher in the lebrikizumab group than in the placebo group (P=0.02). Among patients in the high-periostin subgroup, the increase from baseline FEV(1) was 8.2 percentage points higher in the lebrikizumab group than in the placebo group (P=0.03). Among patients in the low-periostin subgroup, the increase from baseline FEV(1) was 1.6 percentage points higher in the lebrikizumab group than in the placebo group (P=0.61). Musculoskeletal side effects were more common with lebrikizumab than with placebo (13.2% vs. 5.4%, P=0.045).ConclusionsLebrikizumab treatment was associated with improved lung function. Patients with high pretreatment levels of serum periostin had greater improvement in lung function with lebrikizumab than did patients with low periostin levels. (Funded by Genentech; ClinicalTrials.gov number, NCT00930163.)