Nelson David R, Rustgi Vinod, Balan Vijayan, Sulkowski Mark S, Davis Gary L, Muir Andrew J, Lambiase Louis R, Dickson Rolland C, Weisner Russell H, Fiscella Michele, Cronin Patrick W, Pulkstenis Erik, McHutchison John G, Subramanian G Mani
University of Florida College of Medicine, Box 100214, Room M-440, Gainesville, Florida 32610-0214, USA.
Clin Gastroenterol Hepatol. 2009 Feb;7(2):212-8. doi: 10.1016/j.cgh.2008.10.035. Epub 2008 Nov 7.
BACKGROUND & AIMS: Pegylated interferon alfa-2a/2b is used in combination with ribavirin to treat patients with chronic hepatitis C (CHC), although many do not achieve a sustained virologic response (SVR). Albinterferon alfa-2b, a recombinant protein consisting of interferon alfa-2b fused to human albumin, may increase drug exposure. This phase 2 study evaluated the safety/efficacy of albinterferon in CHC patients who had not responded to interferon-based regimens.
A total of 115 patients were assigned to 5 groups given 1200 microg albinterferon every 4 weeks or 900, 1200, 1500, or 1800 microg every 2 weeks, plus oral ribavirin, for 48 weeks. The primary efficacy end point was achievement of an SVR after 24 weeks. Treatment was extended to 72 weeks for 6 slow responders who were negative for hepatitis C virus RNA after 24 weeks.
The types of adverse events were similar across groups; the overall discontinuation rate as a result of adverse events was 10.4%. Reductions in absolute neutrophil counts were less frequent in the every 4 weeks group and comparable among the every 2 weeks groups. The overall SVR rate was 17% (11% for previous nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection). An SVR occurred in 3 of 6 slow responders by 72 weeks. The greatest reductions in hepatitis C virus RNA in nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection were observed in the 1800-microg group.
In patients with CHC who did not respond to interferon-based regimens, higher doses of albinterferon had significant early antiviral activity and a low incidence of adverse events, with the types of adverse events similar to those observed with interferon.
聚乙二醇化干扰素α-2a/2b与利巴韦林联合用于治疗慢性丙型肝炎（CHC）患者，尽管许多患者未实现持续病毒学应答（SVR）。Albinterferon alfa-2b是一种由干扰素α-2b与人白蛋白融合而成的重组蛋白，可能会增加药物暴露。这项2期研究评估了Albinterferon在对基于干扰素的治疗方案无反应的CHC患者中的安全性/疗效。
总共115例患者被分配到5组，每4周给予1200μg Albinterferon或每2周给予900、1200、1500或1800μg，加口服利巴韦林，共48周。主要疗效终点是24周后实现SVR。对24周后丙型肝炎病毒RNA阴性的6例反应缓慢者，治疗延长至72周。
各组不良事件类型相似；因不良事件导致的总体停药率为10.4%。每4周给药组中性粒细胞绝对计数减少的情况较少，每2周给药组之间相当。总体SVR率为17%（1型感染的既往聚乙二醇化干扰素α/利巴韦林无反应者为11%）。6例反应缓慢者中有3例在72周时实现了SVR。在1型感染的聚乙二醇化干扰素α/利巴韦林无反应者中，1800μg组丙型肝炎病毒RNA下降幅度最大。
在对基于干扰素的治疗方案无反应的CHC患者中，较高剂量的Albinterferon具有显著的早期抗病毒活性，不良事件发生率低，不良事件类型与干扰素观察到的相似。
