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.