Authors' objectives:

The aim of this systematic review and economic evaluation was to assess the clinical-effectiveness and cost-effectiveness of pegylated interferon-alpha combined with ribavirin in the treatment of chronic hepatitis C. The comparator was the current standard of treatment, non-pegylated interferon-a combined with ribavirin. Because some patients cannot tolerate ribavirin, treatment with pegylated interferon-alpha alone was also compared with treatment with non-pegylated interferon-a alone. Additional secondary questions were also addressed, including the effectiveness of retreating non-responders to interferon-a monotherapy, the use of non-invasive tests for gauging the severity of disease (e.g. fibrosis), and the effectiveness of antiviral treatment of patients with mild hepatitis C.

Authors' results and conclusions: Dual therapy: In the two trials that tested pegylated interferon plus ribavirin against non-pegylated interferon plus ribavirin the combined percentage of sustained virological response was 55% [95% (confidence interval (CI) 5258%] when using pegylated interferon and 46% (95% CI 4349%) for non-pegylated interferon. When the two trials were meta-analysed the relative risk (RR) for remaining infected was reduced by 17% for pegylated interferon plus ribavirin compared with non-pegylated interferon plus ribavirin (RR 0.83, 95% CI 0.76 to 0.91). Response to therapy varied according to viral genotype. Patients with genotype 1 had the lowest levels of sustained virological response (42% and 46% for pegylated interferon plus ribavirin in the two trials) and patients with genotype 2 or 3 had the highest levels of sustained virological response (82% and 76% for pegylated interferon plus ribavirin in the two trials). There were also variations in sustained virological response according to other prognostic variables such as baseline viral load. Monotherapy: In the four trials that evaluated pegylated interferon monotherapy against non-pegylated interferon the combined sustained virological response rates were 31% (95% CI 27 to 34%) for pegylated interferon and 14% (95% CI 12 to 17%) for non-pegylated interferon. The RR for remaining infected with hepatitis C was reduced by 20% with the use of pegylated interferon (RR 0.80, 95% CI 0.76 to 0.85). As reported in three of the trials, response to therapy varied according to viral genotype. Patients with genotype 1 had the lowest levels of sustained virological response (12%, 14% and 31% for treatment with pegylated interferon in the three trials reporting response by genotype). Only one trial differentiated patients with non-1 genotypes and reported higher response rates in patients with genotype 4, 5, or 6 (60%) than in patients with genotype 2 or 3 (49%) when treated with pegylated interferon. In the two trials that considered prognostic variables, there were also variations in sustained virological response according to other prognostic variables such as baseline viral load. Regimens involving pegylated interferon appear to be fairly well tolerated. Adverse events were reported, but they did not differ substantially from levels of adverse events in regimens involving non-pegylated interferon.

Authors' recommendations: Well-designed RCTs show that patients treated with pegylated interferon, both as dual therapy and as monotherapy, experience higher sustained viral response rates than those treated with non-pegylated interferon. Patients with genotypes 2 and 3 experience the highest response, with rates in excess of 80%. Patients with the harder to treat genotype 1 nevertheless benefit, with up to 46% of patients experiencing an SVR in one of the trials. Pegylated interferon also appears to be relatively cost-effective in both monotherapy and dual therapy, with cost per QALY estimates remaining generally under 30,000 GBP. The most favourable estimates were for patients with genotypes 2 and 3.

Authors' methods: Systematic review, Economic evaluation

Project Status: Completed

URL for project: http://www.hta.ac.uk/1347

Year Published: 2004

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England, United Kingdom

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk

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