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Peginterferon-alpha-2a (40kD) plus ribavirin: a review of its use in the management of chronic hepatitis C.

Abstract
Pegylation of interferon-alpha-2a is associated with improved sustained virological response rates in patients with chronic hepatitis C. Subsequently, combination therapy with peginterferon-alpha-2a (40kD) [Pegasys] and ribavirin (Copegus trade mark, Rebetol) was investigated to establish if the efficacy of peginterferon-alpha-2a (40kD) monotherapy could be further enhanced. Subcutaneous peginterferon-alpha-2a (40kD) was administered at a dosage of 180 micro g once weekly and oral ribavirin was usually administered at a dosage of 1000 or 1200 mg/day. In treatment-naive patients with chronic hepatitis C, the sustained virological response rate (assessed 24 weeks after the end of a 48-week treatment period) was significantly higher in peginterferon-alpha-2a (40kD) plus ribavirin recipients than in peginterferon-alpha-2a (40kD) plus placebo recipients or interferon-alpha-2b plus ribavirin recipients (56% vs 29% and 44%). Retrospective analysis revealed that peginterferon-alpha-2a (40kD) plus ribavirin recipients who did not achieve an early virological response were unlikely to achieve a sustained response. Treatment with peginterferon-alpha-2a (40kD) plus another antiviral agent (ribavirin, mycophenolate mofetil, amantadine, or ribavirin and amantadine) was beneficial in patients with chronic hepatitis C who had relapsed during or after, or had not responded to, treatment with interferon-alpha-2b plus ribavirin. In the relapse study, sustained virological response rates in recipients of peginterferon-alpha-2a (40kD) plus ribavirin were 45% with and 38% without amantadine. Peginterferon-alpha-2a (40kD) plus ribavirin appears beneficial in patients with chronic hepatitis C considered difficult to treat (e.g. patients infected with hepatitis C virus genotype 4, African-American patients, patients with advanced fibrosis or cirrhosis and patients co-infected with HIV). Flu-like symptoms and depression occurred significantly less frequently with peginterferon-alpha-2a (40kD) plus ribavirin than with interferon-alpha-2b plus ribavirin. Similar proportions of patients receiving peginterferon-alpha-2a (40kD) plus ribavirin, peginterferon-alpha-2a (40kD) plus placebo and interferon-alpha-2b plus ribavirin withdrew from treatment because of laboratory abnormalities or other adverse events. In conclusion, combination therapy comprising subcutaneous peginterferon-alpha-2a (40kD) and oral ribavirin is an important new treatment option for chronic hepatitis C. Peginterferon-alpha-2a (40kD) plus oral ribavirin is significantly more effective than peginterferon-alpha-2a (40kD) monotherapy or interferon-alpha-2b plus ribavirin at inducing a sustained virological response in treatment-naive patients with chronic hepatitis C. Preliminary data suggest that peginterferon-alpha-2a (40kD) plus ribavirin is also beneficial in treatment-experienced patients and in patients who have traditionally been considered difficult to treat. Combination therapy with peginterferon-alpha-2a (40kD) and oral ribavirin is poised to become a valuable first-line treatment option in chronic hepatitis C.
AuthorsGillian M Keating, Monique P Curran
JournalDrugs (Drugs) Vol. 63 Issue 7 Pg. 701-30 ( 2003) ISSN: 0012-6667 [Print] New Zealand
PMID12656650 (Publication Type: Journal Article, Review)
Chemical References
  • Antiviral Agents
  • Interferon-alpha
  • Recombinant Proteins
  • peginterferon alfa-2a
  • peginterferon alfa-2b
  • Polyethylene Glycols
  • Ribavirin
  • interferon alfa-2a
  • interferon alfa-2b
Topics
  • Adsorption
  • African Continental Ancestry Group
  • Antiviral Agents (administration & dosage, pharmacokinetics, pharmacology)
  • Drug Interactions
  • Drug Therapy, Combination
  • HIV Infections (complications)
  • Hepatitis C, Chronic (drug therapy)
  • Humans
  • Interferon-alpha (administration & dosage, pharmacokinetics, pharmacology)
  • Liver Cirrhosis (complications)
  • Polyethylene Glycols
  • Quality of Life
  • Recombinant Proteins
  • Ribavirin (administration & dosage, pharmacokinetics, pharmacology)
  • Treatment Outcome

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