Peginterferon-alpha-2a (40kD) plus ribavirin: a review of its use in the management of chronic hepatitis C.
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.
Keating
Gillian M
GM
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Curran
Monique P
MP
D000327:Adsorption; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D044383:Black People; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000150:complications; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000150:complications; D011092:Polyethylene Glycols; D011788:Quality of Life; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D016896:Treatment Outcome; D001741:Black or African American
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a