Elsevier

The Lancet

Volume 358, Issue 9286, 22 September 2001, Pages 958-965
The Lancet

Articles
Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial

https://doi.org/10.1016/S0140-6736(01)06102-5Get rights and content

Summary

Background

A sustained virological response (SVR) rate of 41% has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this randomised trial, peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin.

Methods

1530 patients with chronic hepatitis C were assigned interferon alfa-2b (3 MU subcutaneously three times per week) plus ribavirin 1000–1200 mg/day orally, peginterferon alfa-2b 15 μg/kg each week plus 800 mg/day ribavirin, or peginterferon alfa-2b 1·5 μg/kg per week for 4 weeks then 0·5 μg/kg per week plus ribavirin 1000–1200 mg/day for 48 weeks. The primary endpoint was the SVR rate (undetectable hepatitis C virus [HCV] RNA in serum at 24-week follow-up). Analyses were based on patients who received at least one dose of study medication.

Findings

The SVR rate was significantly higher (p=0·01 for both comparisons) in the higher-dose peginterferon group (274/511 [54%]) than in the lower-dose peginterferon (244/514 [47%]) or interferon (235/505 [47%]) groups. Among patients with HCV genotype 1 infection, the corresponding SVR rates were 42% (145/348), 34% (118/349), and 33% (114/343). The rate for patients with genotype 2 and 3 infections was about 80% for all treatment groups. Secondary analyses identified bodyweight as an important predictor of SVR, prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight (mg/kg). Side-effect profiles were similar between the treatment groups.

Interpretation

In patients with chronic hepatitis C, the most effective therapy is the combination of peginterferon alfa-2b 1·5 μg/kg per week plus ribavirin. The benefit is mostly achieved in patients with HCV genotype 1 infections.

Introduction

Chronic hepatitis C infection affects nearly 300 million people worldwide and is one of the main causes of chronic liver disease and commonest indication for liver transplantation.1, 2, 3, 4, 5, 6 The most effective initial therapy for patients with this disorder is the combination of interferon alfa-2b plus ribavirin given for 24 or 48 weeks. With this two-drug regimen, about 40% of patients achieve a sustained virological response (SVR) and the associated potential long-term benefits.7, 8

The addition of a polyethyleneglycol molecule to interferon produces a biologically active molecule with a longer half-life than the natural molecule and more favourable pharmacokinetics; these characteristics allow for more convenient once-weekly dosing.9 When pegylated a interferons are given alone to patients with chronic hepatitis C for 48 weeks, the SVR rate is approximately twice that with standard interferon.10, 11 However, relapse rates after cessation of monotherapy with pegylated interferon remain high, and most patients infected with hepatitis C virus (HCV) genotype 1 do not achieve SVR.10, 11 Addition of ribavirin to interferon alfa-2b decreases the risk of relapse.7, 8 The addition of ribavirin to peginterferon alfa-2b might therefore be expected to decrease the risk of relapse after therapy.12 This study aimed to assess the safety and efficacy of two different regimens of peginterferon alfa-2b in combination with ribavirin compared with interferon alfa-2b plus ribavirin, and to identify predictors of response for peginterferon alfa-2b plus ribavirin.

Section snippets

Selection of patients

Eligible patients were previously untreated adults who had HCV RNA detectable in serum by PCR, who had undergone a liver biopsy within 1 year before entry that was consistent with chronic hepatitis, and who had high serum values of alanine aminotransferase (above the upper limit of normal >43 IU/L for men, >34 IU/L for women) with minimum haematological and biochemical values of: haemoglobin 120 g/L for women and 130 g/L for men; white-blood-cell count 3×109/L; neutrophil count 1·5·109/L;

References (21)

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