Maher, Toby M. A Costabel, Ulrich A Glassberg, Marilyn K. A Kondoh, Yasuhiro A Ogura, Takashi A Scholand, Mary Beth A Kardatzke, David Howard, Monet A Olsson, Julie A Neighbors, Margaret A Belloni, Paula A Swigris，Jeffrey J. %T 2期临床试验评估lebrikizumab在特发性肺纤维化患者中的疗效和安全性一种白细胞介素(IL)-13单克隆抗体，单独或联合吡非尼酮治疗特发性肺纤维化(IPF)患者。年龄≥40岁的IPF患者，强迫肺活量(FVC)预测为40%-100%，一氧化碳扩散能力预测为25%-90%，患者为treatment-naïve(队列A)或接受吡非尼酮(2403 mg·d - 1;队列B)每4周皮下注射lebrikizumab 250mg或安慰剂。主要终点为预测在52周内下降的年FVC %率。在队列A中，154例患者随机接受lebrikizumab (n=78)或安慰剂(n=76)。在队列B中，351例接受吡非尼酮治疗的患者随机接受lebrikizumab (n=174)或安慰剂(n=177)。两组治疗组的基线人口统计数据是平衡的。在队列A中，主要终点(年化FVC %预测下降率)未达到(lebrikizumab vs安慰剂，- 5.2% vs - 6.2%; p=0.456) or cohort B (lebrikizumab versus placebo, −5.5% versus −6.0%; p=0.557). In cohort B, a non-statistically significant imbalance in mortality favouring combination therapy was observed (hazard ratio 0.42 (95% CI 0.17–1.04)). Pharmacodynamic biomarkers indicated lebrikizumab activity. The safety profile was consistent with that in previous studies of lebrikizumab and pirfenidone as monotherapies.Lebrikizumab alone or with pirfenidone was not associated with reduced FVC % predicted decline over 52 weeks despite evidence of pharmacodynamic activity. Lebrikizumab was well tolerated with a favourable safety profile. These findings suggest that blocking IL-13 may not be sufficient to achieve a lung function benefit in patients with IPF.This phase 2 RCT found no benefit in FVC decline over 52 weeks in IPF patients for lebrikizumab versus placebo as monotherapy (n=78 versus 76) or in combination with pirfenidone (n=174 versus 177); pirfenidone therapy was consistent with previous results https://bit.ly/313NVR8 %U //www.qdcxjkg.com/content/erj/57/2/1902442.full.pdf