Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: A randomized phase 2b study (LIRA-B)
Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: A randomized phase 2b study (LIRA-B)
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DOI：
10.1016/j.jhep.2015.12.018
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发表时间：
2016-05-01
影响因子：
25.7
通讯作者：
Cooney, Elizabeth
中科院分区：
文献类型：
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作者：
Chan, Henry L. Y.;Ahn, Sang Hoon;Cooney, Elizabeth
背景与目的：聚乙二醇干扰素lambda-1a （lambda）是一种iii型干扰素，与α干扰素一样，在体外对乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）具有抗病毒活性；然而，lambda的肝外受体分布更有限。这项2b期研究（LIRA-B）评估了慢性HBV感染患者的lambda。方法：未接受HBeAg+干扰素治疗的成年患者随机（1:1）接受每周一次λ (180 g)或聚乙二醇干扰素α -2a （alfa）治疗，持续48周。主要疗效终点为治疗后第24周的HBeAg血清转化；如果80%置信区间（80% CI）下界为>-15%，则证明lambda非劣效性。结果：各组基线特征平衡（lambda N = 80; alpha N = 83）。在治疗早期，到第24周，lambda的HBV-DNA和qHBsAg下降幅度更大。在第48周，HBeAg的λ和α血清转化率相当（分别为17.5%和16.9%）；然而，lambda在治疗后第24周未达到非劣效性（分别为13.8% vs. 30.1%; lambda vs. alpha 80% CI下限-24%）。其他关键次要终点（病毒学、血清学、生化）和事后联合终点（HBV-DNA）的结果
Background & Aims: Peginterferon lambda-1a (lambda) is a Type-III interferon, which, like alfa interferons, has antiviral activity in vitro against hepatitis B virus (HBV) and hepatitis C virus (HCV); however, lambda has a more limited extra-hepatic receptor distribution. This phase 2b study (LIRA-B) evaluated lambda in patients with chronic HBV infection.Methods: Adult HBeAg+ interferon-naive patients were randomized (1:1) to weekly lambda (180 lug) or peginterferon alfa-2a (alfa) for 48 weeks. The primary efficacy endpoint was HBeAg seroconversion at week 24 post-treatment; lambda non inferiority was demonstrated if the 80% confidence interval (80% CI) lower bound was >-15%.Results: Baseline characteristics were balanced across groups (lambda N = 80; alfa N = 83). Early on-treatment declines in HBV-DNA and qHBsAg through week 24 were greater with lambda. HBeAg seroconversion rates were comparable for lambda and alfa at week 48 (17.5% vs. 16.9%, respectively); however lambda non-inferiority was not met at week 24 post-treatment (13.8% vs. 30.1%, respectively; lambda vs. alfa 80% CI lower bound -24%). Results for other key secondary endpoints (virologic, serologic, biochemical) and post hoc combined endpoints (HBV-DNA