聚乙二醇干扰素α-2a（40kD）与利巴韦林治疗慢性丙型肝炎患者：一项II期开放标签研究。

Peginterferon-alpha-2a (40kD) and ribavirin in patients with chronic hepatitis C: a phase II open-label study.

作者信息

Sulkowski Mark, Reindollar Robert, Thomas David L, Brinkley-Laughton Sherilyn, Hudson Martha, Yu Jian

机构信息

The Johns Hopkins University School of Medicine, 1830 East Monument Street, Rm 448, Baltimore, MD 21267-0003, USA.

出版信息

BioDrugs. 2002;16(2):105-9. doi: 10.2165/00063030-200216020-00004.

DOI:10.2165/00063030-200216020-00004

PMID:11985484

Abstract

BACKGROUND AND AIMS

Addition of a 40kD polyethylene glycol moiety to interferon-alpha-2a [peginterferon-alpha-2a (40kD)] improves pharmacokinetic properties over those of standard interferon. We conducted a phase II study to assess the safety and initial efficacy of peginterferon-alpha-2a (40kD) plus ribavirin combination therapy in patients with chronic hepatitis C (CHC).

METHODS

Twenty patients received open-label 180 microg peginterferon-alpha-2a (40kD) subcutaneously once weekly and oral ribavirin 1000 or 1200mg daily for patients weighing <75 or > or =75kg, respectively, for a period of 24 weeks. Patients with hepatitis C virus (HCV) genotype 1 and a virological response at week 24 received study drugs for an additional 24 weeks.

RESULTS

A sustained virological response, defined as undetectable HCV RNA 24 (i.e. <100 copies/ml) weeks after completing the therapy, was achieved in 50% of patients in an intent-to-treat analysis (6/16 genotype 1 and 4/4 genotype non-1). Adverse events were similar to those reported with unmodified interferon plus ribavirin combination therapy. Anaemia led to ribavirin dose reduction in five patients. Neutropenia led to dose reduction in three patients treated with peginterferon-alpha-2a (40kD).

CONCLUSIONS

The addition of ribavirin to a once-weekly peginterferon-alpha-2a (40kD) regimen should be investigated in larger clinical trials.

摘要

背景与目的

在干扰素α-2a上添加一个40kD的聚乙二醇部分[聚乙二醇化干扰素α-2a（40kD）]，相对于标准干扰素，可改善药代动力学特性。我们开展了一项II期研究，以评估聚乙二醇化干扰素α-2a（40kD）联合利巴韦林治疗慢性丙型肝炎（CHC）患者的安全性和初始疗效。

方法

20例患者接受开放标签治疗，皮下注射180μg聚乙二醇化干扰素α-2a（40kD），每周1次，体重<75kg或≥75kg的患者分别口服利巴韦林每日1000mg或1200mg，疗程为24周。丙型肝炎病毒（HCV）基因1型且在第24周出现病毒学应答的患者再接受24周的研究药物治疗。

结果

在意向性分析中，50%的患者实现了持续病毒学应答，定义为完成治疗后24周（即<100拷贝/ml）检测不到HCV RNA（基因1型患者中6/16例，非1型基因患者中4/4例）。不良事件与未修饰的干扰素联合利巴韦林治疗报道的相似。贫血导致5例患者减少利巴韦林剂量。中性粒细胞减少导致3例接受聚乙二醇化干扰素α-2a（40kD）治疗的患者减少剂量。