Low- and standard-dose peginterferon alfa-2a for chronic hepatitis C, genotype 2 or 3: efficacy, tolerability, viral kinetics and cytokine response

Aliment Pharmacol Ther. 2010 May;31(9):1018-27. doi: 10.1111/j.1365-2036.2010.04263.x. Epub 2010 Jan 16.

Abstract

Background: Chronic infection with hepatitis C, genotype 2/3, responds better than other genotypes to peginterferon and ribavirin treatment. We hypothesized that a lower dose of peginterferon would be as effective, but less toxic than standard doses.

Aim: To test the hypothesis that a lower dose of peginterferon would be as effective as, but less toxic than, standard doses.

Methods: A total of 30 patients were treated with low-dose peginterferon alfa-2a (90 microg/week) and 27 patients with standard doses (180 microg/week) for 24 weeks in combination with 800 mg/day of ribavirin. Patients who failed treatment were offered 48 weeks of standard-dose treatment. Viral and serum inducible protein 10 (IP-10) levels were measured and early viral kinetic parameters were calculated.

Results: Sustained virological response was achieved in 68% of the low-dose and 87% of the standard-dose patients (per protocol, P = 0.79 for non-inferiority). Re-treatment was successful in all patients who tolerated full dose and duration. The standard-dose group had greater first-phase declines of viral levels and faster time to negativity. The second-phase slope was not dose-dependent. IP-10 induction was significantly greater with the standard dose. Although fatigue and general feeling during treatment were worse for standard dose, haematological toxicity and depression did not differ between groups.

Conclusion: A lower dose of peginterferon is associated with some symptomatic benefit, but the response is not equivalent to standard dosing.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage*
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • RNA, Messenger / metabolism
  • Recombinant Proteins
  • Ribavirin / administration & dosage*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Cytokines
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Messenger
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a