Interferon-alpha-2b plus ribavirin: a review of its use in the management of chronic hepatitis C.
Relatively few patients (< or =20%) with chronic hepatitis C achieve a sustained virological response after interferon-alpha monotherapy. Hence, alternative treatment strategies such as the addition of the broad spectrum antiviral agent ribavirin to interferon-alpha-2b have been investigated. Combination therapy with subcutaneous interferon-alpha-2b [3 million units (MU) three times per week] plus oral ribavirin (1000 to 1200 mg/day) has proven effective in several well designed trials of 24 to 48 weeks' duration in adult patients with compensated chronic hepatitis C. Compared with interferon-alpha-2b (3 or 6 MU three times per week) with or without placebo, combination treatment with interferon-alpha-2b plus ribavirin significantly enhanced end-of-treatment and sustained virological and biochemical response rates in treatment-naive and treatment-experienced patients [sustained virological response rates in treatment-naive recipients (6 to 19% vs 31 to 43% of patients); sustained overall (virological plus biochemical) response rates in nonresponders to (1 vs 14%) or relapsers (4 to 5% vs 30 to 44%) after previous interferon-alpha monotherapy]. Forty-eight weeks of combination therapy was superior to 24 weeks in treatment-naive patients infected with hepatitis virus C (HCV) genotype 1, whereas response rates were similar at 24 and 48 weeks in those infected with other HCV genotypes. Furthermore, there were marked improvements in histological inflammatory scores in patients who responded to treatment with either interferon-alpha-2b plus ribavirin or interferon-alpha-2b alone. Although adverse events associated with either drug during combination therapy occurred frequently, these were generally mild to moderate in intensity and were consistent with those reported for each individual agent. Twenty-six percent of patients required dosage modifications of one or both drugs during combination therapy.


CONCLUSIONS
Interferon-alpha-2b plus ribavirin is an efficacious first- and second-line therapy in adult patients with compensated chronic hepatitis C, significantly improving sustained virological and biochemical responses versus interferon-alpha-2b monotherapy. The tolerability profile of interferon-alpha-2b plus ribavirin therapy is consistent with the individual profiles of these agents with no evidence of additive effects. The place of interferon-alpha-2b plus ribavirin combination therapy in relation to newer agents, including pegylated interferons-alpha and other multidrug regimens, remains to be determined in this rapidly evolving area of therapeutic management. Currently, combination therapy with interferon-alpha-2b plus ribavirin is recommended as first-line therapy for patients with chronic hepatitis C and compensated liver disease, and is an option for use as second-line therapy in those who have relapsed after, or failed to respond to, previous treatment with interferon-alpha.
Scott
Lesley J
LJ
Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand. demail@adis.co.nz
Perry
Caroline M
CM
D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D000743:Anemia, Hemolytic / Q000139:chemically induced; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D019964:Mood Disorders / Q000139:chemically induced; D011994:Recombinant Proteins; D012254:Ribavirin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin