In an RCT 1, patients with chronic hepatitis C received either 180 mcg of peginterferon alfa-2a subcutaneously once per week for 48 weeks (n=267) ) or 6 million units of interferon alfa-2a s.c. three times per week for 12 weeks, followed by 3 million units three times per week for 36 weeks (n=264). Peginterferon was associated with a higher rate of virologic response at week 48 (69% vs. 28%, p=0.001) and at week 72 (39% vs. 19%, p=0.001; intention-to-treat analysis). Sustained normalization of serum alanine aminotransferase concentrations at week 72 was also more common in the peginterferon group (45% vs. 25%, p=0.001).
In another trial 2, HCV RNA was undetectable at week 72 in 8 percent, 15 percent, and 30 percent of the patients treated with interferon alfa-2a and with 90 mcg and 180 mcg of peginterferon alfa-2a, respectively (intention-to-treat analysis; p=0.001 for the comparison between 180 microg of peginterferon alfa-2a and interferon alfa-2a). At week 72, alanine aminotransferase concentrations had normalized in 15 percent, 20 percent, and 34 percent of patients, respectively.
A technology assessment report 3 on antiviral therapies for chronic hepatitis C was abstracted in the Health Technology Assessment Database. Pegylated interferon (Peg-IFN) results in a sustained response (i.e., undetectable hepatitis C virus RNA 6 months after treatment) in approximately 25-39% of the patients treated, as compared to 20% for IFN treatment. Peg-IFN and ribavirin combined have shown sustained response rates of approximately 54% as compared to 42% to 47% for IFN and ribavirin treatment. For patients with compensated cirrhosis or fibrosis, sustained response rates have ranged from 17% (IFN plus ribavirin) to 30% (Peg-IFN). Patients who achieve a sustained response are likely to maintain the response permanently and are likely to show regression of histologic changes in the liver. Virus genotype is the most important predictor of achieving a sustained response. Additional predictors include presence of cirrhosis and HCV RNA level. Peg-IFN and the combination of Peg-IFN and ribavirin are generally safe when closely monitored in an experienced center. Serious side effects occur in 7-14% of cases.
Another technology assessment report 4 included 6 RCTs: 2 on combination therapy (n=2 651) and 4 on monotherapy (n=2 180). The trials were generally of a good quality. In combination therapy, the combined percentage of sustained virological response was 55% (95% CI 52-58) using pegylated IFN and 46% (95% CI 43-49) using non-pegylated IFN. The relative risk (RR) for remaining infected was reduced for pegylated in comparison with non-pegylated IFN (RR 0.83, 95% CI 0.76-0.91). There was no evidence of statistical heterogeneity (P=0.29; I-squared 12%). In monotherapy, the combined percentage of sustained virological response was 31% (95% CI 27-34) for pegylated IFN and 14% (95% CI 12-17) for non-pegylated IFN. The RR for remaining infected was reduced for pegylated in comparison with non-pegylated IFN (RR 0.80, 95% CI 0.76-0.85). There was evidence of statistical heterogeneity (P=0.03; I-squared 66.6%). For both combination and monotherapy, treatment response varied according to viral genotype and other prognostic variables, including baseline viral load. Adverse events with pegylated IFN were not substantially different from the rates of adverse events observed with non-pegylated IFN.
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