JW Goethe University Hospital, Frankfurt, Germany.
Gastroenterology. 2010 Oct;139(4):1257-66. doi: 10.1053/j.gastro.2010.06.066. Epub 2010 Jun 27.
BACKGROUND & AIMS: The current standard of care for patients with chronic hepatitis C virus (HCV) genotype 1 is once-weekly pegylated interferon-α (Peg-IFNα) plus daily ribavirin for 48 weeks. We evaluated the efficacy/safety of albinterferon alfa-2b (albIFN), a novel, long-acting, genetic fusion polypeptide of albumin and IFNα-2b.
In the phase 3 ACHIEVE-1 trial, 1331 patients were assigned equally to 3 open-label, 48-week treatment groups: Peg-IFNα-2a 180 μg every week, or albIFN 900 or 1200 μg every 2 weeks administered subcutaneously, with weight-based oral ribavirin 1000-1200 mg/day. During the study, the data monitoring committee recommended dose modification for all patients receiving albIFN 1200 μg to 900 μg because of increased pulmonary adverse events (AEs) in the 1200-μg arms of both ACHIEVE studies. Main outcome measure was sustained virologic response (SVR; undetectable serum HCV RNA at week 72).
Intention-to-treat SVR rates were 51.0% (225/441), 48.2% (213/442), and 47.3% (208/440) with Peg-IFNα-2a, and albIFN 900 and 1200 μg, respectively. The primary objective of showing noninferiority of albIFN 900 μg (P < .001) and 1200 μg (P = .003) vs Peg-IFNα-2a for SVR was achieved. Multivariate modeling indicated consistency of treatment effect across subgroups. Serious/severe AE rates were 23.1%, 24.0%, 28.2%; treatment discontinuation rates because of AEs were 4.1%, 10.4%, 10.0%; discontinuation rates because of respiratory AEs were 0%, 0.9%, 1.6%; with Peg-IFNα-2a, and albIFN 900 and 1200 μg, respectively. Hematologic abnormality rates were comparable across the Peg-IFNα-2a and albIFN 900-μg groups.
albIFN 900 μg every 2 weeks showed comparable efficacy, with similar serious/severe AE rates, although with a higher discontinuation rate, vs Peg-IFNα-2a in patients with chronic HCV genotype 1.
目前，慢性丙型肝炎病毒（HCV）基因型 1 患者的标准治疗方案为每周一次聚乙二醇干扰素-α（Peg-IFNα）联合每日利巴韦林治疗 48 周。我们评估了新型长效基因融合蛋白白蛋白-干扰素α-2b（albIFN）在治疗中的疗效/安全性。
在 3 期 ACHIEVE-1 试验中，1331 例患者被平均分为 3 组，接受为期 48 周的开放性治疗：每周接受 Peg-IFNα-2a 180 μg，或每 2 周皮下注射 albIFN 900 或 1200 μg，同时每日口服利巴韦林 1000-1200 mg，基于体重。研究期间，数据监测委员会建议所有接受 albIFN 1200 μg 治疗的患者将剂量减少至 900 μg，因为在 ACHIEVE 研究的 albIFN 1200 μg 双臂中均发生了更多的肺部不良事件（AE）。主要观察终点为持续病毒学应答（SVR；治疗 72 周时血清 HCV RNA 不可检测）。
意向治疗 SVR 率分别为 Peg-IFNα-2a 组 51.0%（225/441）、albIFN 900 μg 组 48.2%（213/442）和 albIFN 1200 μg 组 47.3%（208/440）。albIFN 900 μg（P<0.001）和 1200 μg（P=0.003）与 Peg-IFNα-2a 相比非劣效性的主要目标得到了证实。多变量模型表明治疗效果在各亚组中具有一致性。严重/重度 AE 发生率分别为 23.1%、24.0%和 28.2%；因 AE 而停药的发生率分别为 4.1%、10.4%和 10.0%；因呼吸系统 AE 而停药的发生率分别为 0%、0.9%和 1.6%；分别为 Peg-IFNα-2a 和 albIFN 900 和 1200 μg 组。Peg-IFNα-2a 组和 albIFN 900 μg 组的血液学异常发生率相当。
albIFN 900 μg 每 2 周 1 次的疗效与 Peg-IFNα-2a 相当，严重/重度 AE 发生率相似，但因 AE 停药率更高，在慢性 HCV 基因型 1 患者中，albIFN 900 μg 是 Peg-IFNα-2a 的一种替代治疗方案。
