Albinterferon alfa-2b dosed every two or four weeks in interferon-naive patients with genotype 1 chronic hepatitis C
Albinterferon alfa-2b dosed every two or four weeks in interferon-naive patients with genotype 1 chronic hepatitis C
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DOI：
10.1002/hep.22403
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发表时间：
2008-08-01
期刊：
影响因子：
13.5
通讯作者：
McHutchison, John G.
中科院分区：
文献类型：
--
作者：
Zeuzein, Stefan;Yoshida, Eric M.;McHutchison, John G.
alb-interferon alfa-2b (alb-IFN) 是一种由干扰素 alfa-2b 与人白蛋白基因融合组成的新型重组蛋白，在一项针对基因型 1 慢性丙型肝炎患者的 2b 期开放标签研究中评估了其有效性和安全性。总共，458 名未接受过 IFN-alfa 治疗的患者被随机分配接受为期 48 周的聚乙二醇干扰素 alfa 治疗 (PEG-IFN α)-2a 180 μg 每周一次 (qwk)，或 alb-IFN 900 或 1,200 μg 每两周一次 (q2wk)，或 1,200 μg 每四周一次 (q4wk)，皮下注射，加上基于体重的口服利巴韦林 1,000 或 1,200 mg/天。通过实时聚合酶链式反应测量丙型肝炎病毒RNA（检测限：10 IU/mL）。主要疗效终点是持续病毒学应答（治疗结束后 24 周丙型肝炎病毒 RNA < 10 IU/mL）。根据意向治疗分析，alb-IFN 900 μg 每两周一次的持续病毒学缓解率为 58.5% (69/118)，1,200 μg 每两周一次的持续病毒学缓解率为 55.5% (61/110)，1,200 μg 每 4 周一次的持续病毒学缓解率为 50.9% (59/116)，以及 57.9% (66/114)与 PEG-IFN α-2a (P = 0.64（整体测试）。 alb-IFN 900 μg q2wk 组因不良事件导致的停药率为 9.3%，1,200 μg q2wk 组为 18.2%，1,200 μg q4wk 组为 12.1%，PEG-IFN α-2a 组为 6.1%（P = 0.04）。每四周组的血液学减少量最低，其他组之间具有可比性。第 12 周时，与 PEG-IFN α-2a 相比，使用 alb-IFN 900 μg q2wk 治疗相关的平均缺勤天数显着较低（1.1 天与 4.3 天；P = 0.006）。结论：与 PEG-IFN α-2a 相比，每 2 周或每 4 周施用 Alb-IFN 可能会提供相当的疗效，并且给药方案有所改进。
The efficacy and safety of albinterferon alfa-2b (alb-IFN), a novel recombinant protein consisting of interferon alfa-2b genetically fused to human albumin, was evaluated in a phase 2b, open-label study of patients with genotype 1, chronic hepatitis C. In all, 458 IFN-alfa treatment-naive patients were randomized to 48-week treatment with peginterferon alfa (PEG-IFN alpha)-2a 180 mu g one time per week (qwk), or alb-IFN 900 or 1,200 mu g once every two weeks (q2wk), or 1,200 mu g once every four weeks (q4wk), administered subcutaneously, plus weight-based oral ribavirin 1,000 or 1,200 mg/day. Hepatitis C virus RNA was measured by real-time polymerase chain reaction (limit of detection: 10 IU/mL). The primary efficacy endpoint was sustained virologic response (hepatitis C virus RNA < 10 IU/mL 24 weeks after the end of treatment). By intention-to-treat analysis, sustained virologic response rates were 58.5% (69/118) with alb-IFN 900 mu g q2wk, 55.5% (61/110) with 1,200 mu g q2wk, and 50.9% (59/116) with 1,200 mu g q4wk, and 57.9% (66/114) with PEG-IFN alpha-2a (P = 0.64 for overall test). Discontinuation rates due to adverse events were 9.3% with alb-IFN 900 mu g q2wk, 18.2% with 1,200 mu g q2wk and 12.1% with 1,200 mu g q4wk, and 6.1% with PEG-IFN alpha-2a (P = 0.04). Hematologic reductions were lowest in the q4wk group and comparable across other groups. At week 12, mean treatment-associated missed workdays were significantly lower with alb-IFN 900 mu g q2wk versus PEG-IFN alpha-2a (1.1 versus 4.3 days; P = 0.006). Conclusion: Alb-IFN administered q2wk or q4wk may offer comparable efficacy, with an improved dosing schedule, compared with PEG-IFN alpha-2a.