Reduced dose and duration of peginterferon alfa-2b and weight-based ribavirin in patients with genotype 2 and 3 chronic hepatitis C

被引:48
作者
Manns, Michael [1 ]
Zeuzem, Stefan [2 ]
Sood, Ajit [3 ]
Lurie, Yoav [4 ]
Cornberg, Markus [1 ]
Klinker, Hartwig [5 ]
Buggisch, Peter [6 ]
Roessle, Martin [7 ]
Hinrichsen, Holger
Merican, Ismail [8 ]
Ilan, Yaron [9 ]
Mauss, Stefan [10 ]
Abu-Mouch, Saif [11 ]
Horban, Andryes [12 ,13 ]
Mueller, Thomas H. [14 ]
Welsch, Christoph [2 ]
Chen, Rongdean [15 ]
Faruqi, Rab [15 ]
Pedicone, Lisa D. [15 ]
Wedemeyer, Heiner [1 ]
机构
[1] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30625 Hannover, Germany
[2] JW Goethe Univ Hosp, Dept Med 1, Frankfurt, Germany
[3] Dayanand Med Coll & Hosp, Ludhiana, Punjab, India
[4] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel
[5] Univ Wurzburg, Med Ctr, Dept Internal Med 2, Div Infect Dis, Wurzburg, Germany
[6] Liver Ctr Hamburg, IFI Inst, Hamburg, Germany
[7] Ctr Ambulatory Gastroenterol & Endocrinol, Freiburg, Germany
[8] Selayang Hosp, Selangor, Malaysia
[9] Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Med, Jerusalem, Israel
[10] Ctr HIV & Hepatogastroenterol, Dusseldorf, Germany
[11] Hillel Yaffe Med Ctr, Hadera, Israel
[12] Warsaw Med Univ, Warsaw, Poland
[13] Hosp Infect Dis, Warsaw, Poland
[14] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany
[15] Merck & Co Inc, Whitehouse Stn, NJ USA
关键词
Hepatitis C; Randomized controlled trial; Noninferiority; Drug therapy; Whites; Asians; PLUS RIBAVIRIN; HCV GENOTYPE-2; MANAGEMENT; DIAGNOSIS; EFFICACY;
D O I
10.1016/j.jhep.2010.12.024
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: There is increasing interest in identifying patients with chronic hepatitis C genotype 2 or 3 infection in whom it is possible to lower the burden of therapy while retaining high levels of efficacy. Methods: Treatment-naive patients with chronic hepatitis C genotype 2/3 infection were randomized to receive peginterferon alfa-2b (1.5 mu g/kg/wk) for 24 weeks (group A); peginterferon alfa-2b (1.0 mu g/kg/wk) for 24 weeks (group B); or peginterferon alfa-2b (1.5 mu g/kg/wk) for 16 weeks (group C), each in combination with weight-based ribavirin (800-1200 mg/d). The study population comprised two cohorts: the Hep-Net cohort enrolled in Germany and an International cohort enrolled at study sites throughout Europe and Asia. The primary end point was sustained virological response (SVR). Results: The study included 682 patients; 80.2% had genotype 3 infection. In the intent-to-treat population, SVR rates were 66.5%, 64.3%, and 56.6% in groups A, B, and C, and were similarin Asian and white patients. Treatment differences (A vs. B and A vs. C) failed to reach the predefined margin for noninferiority of -10%; and thus groups B and C failed to show noninferiority relative to group A. Among patients with undetectable HCV RNA at week 4, SVR rates were 75.3%, 75.9%, and 72.4%, respectively. Relapse rates were 17.8%, 16.3%, and 29.3%, respectively. Treatment-emergent serious adverse events were highest in group A and lowest in group C, and adverse events leading to discontinuation were similar across treatment arms. Conclusions: For patients with chronic hepatitis C genotype 2/3 infection, 24 weeks of peginterferon alfa-2b (1.5 mu g/kg/wk) plus weight-based ribavirin remains a standard-of-care therapy; however, treatment for 16 weeks may be considered for patients with undetectable HCV RNA at week 4 of the treatment. (C) 2011 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
引用
收藏
页码:554 / 563
页数:10
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