Randomised clinical trial: the efficacy of treatment, guided by a shorter duration of response, using peginterferon alfa-2a plus ribavirin for hepatitis C virus other than genotypes 2 or 3

Aliment Pharmacol Ther. 2012 Jan;35(1):37-47. doi: 10.1111/j.1365-2036.2011.04911.x. Epub 2011 Nov 2.

Abstract

Background: The efficacy of individualised antiviral treatment durations for chronic hepatitis C remains unclear.

Aim: To evaluate treatment durations based on virological responses at week 4, 8 and 12 of peginterferon alfa-2a plus ribavirin therapy.

Methods: Previously untreated patients with HCV genotypes, other than 2 or 3, initiated therapy with peginterferon alfa-2a 180 μg/week plus ribavirin 1000-1400 mg/day. HCV-RNA-negative patients at week 4 rapid virological response (RVR) were randomised to 24 or 48 weeks of treatment; those negative at week 8 were randomised to 36 or 48 weeks; and those who were negative or had a ≥ 2-log drop at week 12 were randomised to 72 or 48 weeks. Sustained virological response (SVR) was defined as undetectable HCV-RNA after 24 weeks of follow-up.

Results: The study was terminated prematurely due to lagging enrollment. Of 236 patients who started treatment, 195 were randomised at week 4 (n = 50), 8 (n = 61) or 12 (n = 84). Ninety-five per cent of patients had genotype 1. SVR rates were not significantly different between patients randomised to 24 (84%) or 48 weeks (84%) at week 4, to 36 (73%) or 48 weeks (74%) at week 8, or to 48 (49%) or 72 weeks (40%) at week 12.

Conclusions: In this predominantly genotype 1 cohort, shortening therapy to 24 weeks in patients with a week-4 response and 36 weeks in those with a week-8 response produced SVR rates that were similar to a 48-week regimen. Lengthening treatment to 72 weeks did not improve SVR rates. Genotype 1 patients with RVR can be treated for 24 weeks.

Trial registration: ClinicalTrials.gov NCT00483938.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage*
  • Canada
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / genetics
  • Hepacivirus / pathogenicity
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Humans
  • Interferon-alpha / administration & dosage*
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Recombinant Proteins / administration & dosage
  • Ribavirin / administration & dosage*
  • Time Factors
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT00483938