Interferon alfa-2a resembles other recombinant alpha inter-2a has recently been approved by the Food and Drug Administration for use as therapy of chronic hepatitis C in a regimen ferons in structure and pharmacology. Studies delineating its efficacy suggest that after 6 to 12 months of therapy, sustained of 3 million units (MU) three times weekly for 12 months.
It can be given intramuscularly or subcutaneously. biochemical responses occur in 4% to 49% of patients, providing adequate doses (Β’3 million units three times weekly) are
This review summarizes the results of therapeutic trials of interferon alfa-2a in the treatment of chronic hepatitis C, used. Overall, a dose-response curve is evident in regard to biochemical responses, decrease in histological scores for in-focusing on the effect of dose, length of treatment, and other factors that determine initial and sustained responses to this flammation, and virological responses (percent negative serum hepatitis C virus [HCV] RNA) after treatment. Differ-agent. Criteria for evaluating responses to treatment in these studies were comprised of primary responses (biochemical) ences in response rates between studies probably reflect patient selection and particularly the percent of patients with and secondary responses (virological and histological). 1,3 Several studies reported were performed before the availabil-established cirrhosis, because these patients respond less well than those with earlier histological stages of disease. A variety ity of tests for antibody to hepatitis C virus (anti-HCV), and thus were conducted in patients with the clinical diagnosis of regimens of interferon alfa-2a have been used, including use of higher doses, longer periods of treatment, induction of non-A, non-B hepatitis. Retrospective testing has revealed that virtually all patients (96%) were positive for anti-HCV. using higher doses initially, and intermittent pulse therapy. Both longer periods of therapy and induction dosing show Similarly, many of the studies reviewed here were conducted before the availability of reliable assays for the detection of strong but not significant trends toward improvement in response rates, which reach significance when the two strategies hepatitis C virus (HCV) RNA. Limited results from retrospective testing for HCV RNA are now available using carefully are combined. Outcome is not significantly improved by escalating doses during therapy when inadequate responses are preserved samples from earlier European studies (0.10013 and 0.10018). These data were obtained from more than seen, or by pulse therapy. The side effect profile of interferon alfa-2a is similar to that of other interferons. Long-term follow-2,200 serum samples, collected from 317 patients, and tested by the Amplicor-HCV quantitative reverse-transcription up studies have demonstrated that 90% of patients with a sustained biochemical response at 6 months after therapy polymerase chain reaction (PCR) assay (Roche Diagnostic Systems, Inc, Somerville, NJ). 3 Despite certain limitations, maintain the response, and 95% remain negative for HCV RNA in serum. Challenges for the future include better delin-the combined results of these studies provide useful information on treatment responses and outcome. eation of the advantages of induction dosing, the optimal duration of therapy, and further understanding of the frequent STUDY POPULATIONS discordance between HCV RNA data and aminotransferase levels. This latter finding suggests that use of both parameters This review comprises the initial interferon alfa-2a regisis necessary to evaluate fully responses to therapy. (HEPATOLtration studies (not published in full) including more than OGY 1997;26(Suppl 1):89S-95S.)
1,700 patients treated at sites in Europe, the United States, Australia, Canada, Brazil, and Israel, 1 plus postmarketing Interferon alfa-2a (Roferon-A; Hoffmann-La Roche, Nutstudies mainly from Europe. Detailed results from a recently ley, NJ) is a recombinant alpha interferon made by recombiconducted United States trial that included 422 patients nant techniques in Escherichia coli. It has both antiviral and treated with interferon alfa-2a for 24 to 48 weeks are not yet immunomodulatory effects demonstrated both in vitro and in available and will be reported elsewhere. In the early studies, vivo. Pharmacologic and pharmacokinetic observations have 56 placebo recipients and 74 untreated patients were also determined that the activity of interferon alfa-2a closely reevaluated. Criteria for diagnosis of chronic hepatitis C insembles that of other alpha interferons; indeed, it differs from cluded clinical histories suggesting disease for greater than interferon alfa-2b by one amino acid only. 1,2 Interferon alfa-6 months, a liver biopsy consistent with the diagnosis of chronic hepatitis, abnormal alanine aminotransferase (ALT) levels (ΓΊ1.5 times the upper limit of normal), and in most instances, the presence of anti-HCV. Patients were adults Abbreviations: MU, million units; HCV, hepatitis C virus; PCR, polymerase chain between the ages of 18 and 81 years (mean age, 45 years), reaction; ALT, alanine amino transferase; HAI, histology activity index.
had no other confounding illnesses, no evidence of other From the Liver Division,