A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C

被引:525
作者
Lindsay, KL
Trepo, C
Heintges, T
Shiffman, ML
Gordon, SC
Hoefs, JC
Schiff, ER
Goodman, ZD
Laughlin, M
Yao, RJ
Albrecht, JK
机构
[1] Univ So Calif, Ambulatory Hlth Ctr, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA
[2] Hotel Dieu, Lyon, France
[3] Inserm U271, Lyon, France
[4] Univ Dusseldorf, D-4000 Dusseldorf, Germany
[5] Med Coll Virginia, Richmond, VA USA
[6] William Beaumont Hosp, Royal Oak, MI 48072 USA
[7] Univ Calif Irvine, Irvine, CA USA
[8] Univ Miami, Sch Med, Miami, FL USA
[9] Armed Forces Inst Pathol, Washington, DC 20306 USA
[10] Schering Plough Res Inst, Kenilworth, NJ USA
关键词
D O I
10.1053/jhep.2001.26371
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared peginterferon alfa-2b (PegIntron (TM)) to interferon alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon alfa-2b dose (3 MIQ or the once-weekly (QW) peginterferon alfa-2b (0.5, 1.0, or 1.5 mug/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 peginterferon alfa-2b doses significantly (P less than or equal to .042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not dose-related above 1.0 mug/kg peginterferon alfa-2b because of a higher relapse rate among patients treated with 1.5 mug/kg peginterferon alfa-2b, particularly among patients infected with genotype 1. All 3 peginterferon alfa-2b doses decreased liver inflammation to a greater extent than did interferon alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, peginterferon alfa-2b maintained (0.5 mug/kg) or surpassed (1.0, 1.5 mug/kg) the clinical efficacy of interferon alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 mug/kg peginterferon alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation.
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页码:395 / 403
页数:9
相关论文
共 31 条
[1]   The direct interplay between HCVNS5A protein and interferon transduction signal: from clinical to basic science [J].
Brechot, C .
JOURNAL OF HEPATOLOGY, 1999, 30 (06) :1152-1154
[2]   GENETIC-HETEROGENEITY OF HEPATITIS-C VIRUS - QUASI-SPECIES AND GENOTYPES [J].
BUKH, J ;
MILLER, RH ;
PURCELL, RH .
SEMINARS IN LIVER DISEASE, 1995, 15 (01) :41-63
[3]   Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein [J].
Gale, MJ ;
Korth, MJ ;
Tang, NM ;
Tan, SL ;
Hopkins, DA ;
Dever, TE ;
Polyak, SJ ;
Gretch, DR ;
Katze, MG .
VIROLOGY, 1997, 230 (02) :217-227
[4]   A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C [J].
Glue, P ;
Rouzier-Panis, R ;
Raffanel, C ;
Sabo, R ;
Gupta, SK ;
Salfi, M ;
Jacobs, S ;
Clement, RP .
HEPATOLOGY, 2000, 32 (03) :647-653
[5]   Reducing the immunogenicity and improving the in vivo activity of trichosanthin by site-directed PEGylation [J].
He, XH ;
Shaw, PC ;
Tam, SC .
LIFE SCIENCES, 1999, 65 (04) :355-368
[6]   Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis [J].
Heathcote, EJ ;
Shiffman, ML ;
Cooksley, WGE ;
Dusheiko, GM ;
Lee, SS ;
Balart, L ;
Reindollar, R ;
Reddy, RK ;
Wright, TL ;
Lin, A ;
Hoffman, J ;
De Pamphilis, J .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (23) :1673-1680
[7]   SERIAL ASSAY OF HEPATITIS-C VIRUS-RNA IN SERUM FOR PREDICTING RESPONSE TO INTERFERON-ALPHA THERAPY [J].
HINO, K ;
OKUDA, M ;
KONISHI, T ;
ISHIKO, H ;
OKITA, K .
DIGESTIVE DISEASES AND SCIENCES, 1995, 40 (01) :14-20
[8]   BIOMEDICAL AND BIOTECHNOLOGICAL APPLICATIONS OF PEG-MODIFIED AND PM-MODIFIED PROTEINS [J].
INADA, Y ;
FURUKAWA, M ;
SASAKI, H ;
KODERA, Y ;
HIROTO, M ;
NISHIMURA, H ;
MATSUSHIMA, A .
TRENDS IN BIOTECHNOLOGY, 1995, 13 (03) :86-91
[9]  
KATRE NV, 1990, J IMMUNOL, V144, P209
[10]   DETECTION OF HEPATITIS-C VIRUS-RNA IN PATIENTS WITH CHRONIC HEPATITIS-C VIRUS-INFECTIONS DURING AND AFTER THERAPY WITH ALPHA INTERFERON [J].
KLETER, GEM ;
BROUWER, JT ;
HEIJTINK, RA ;
SCHALM, SW ;
QUINT, WGV .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1993, 37 (03) :595-597