Pegylated interferons for chronic hepatitis C virus infection: an indirect analysis of randomized trials

Summary.  Dual therapy with pegylated interferon and ribavirin is recommended for patients with chronic hepatitis C virus infection who meet criteria for treatment, but it is unclear whether pegylated interferon alfa-2a or pegylated interferon alfa-2b is more effective or associated with fewer adverse events. Because data from head-to-head trials of pegylated interferon regimens are sparse, we performed adjusted indirect analysis using trials comparing dual therapy with pegylated interferon alfa-2a or pegylated interferon alfa-2b vs dual therapy with non-pegylated interferon. We searched for potentially relevant randomized controlled trials using electronic databases and reference lists. A total of 16 trials met inclusion criteria. Adjusted indirect comparisons found no statistically significant differences between dual therapy with pegylated interferon alfa-2a and dual therapy with pegylated interferon alfa-2b on the outcomes sustained virologic response [relative risk (RR) = 1.59, 95% CI: 0.56–4.46], withdrawal due to adverse events (RR = 0.86, 95% CI: 0.29–2.55), anaemia (RR = 1.67, 95% CI: 0.32–8.84), depression (RR = 1.09, 95% CI: 0.41–2.90) or flu-like symptoms (RR = 1.10, 95% CI: 0.53–2.29). Adjusting for potential publication bias and stratifying analyses by indicators of methodological quality, human immunodeficiency virus infection status, hepatitis C virus genotype, dose of ribavirin or dose of pegylated interferon did not change conclusions. There is insufficient evidence to support conclusions that dual therapy with one pegylated interferon is superior to the other. However, because estimates are imprecise, our results also do not rule out a clinically significant difference. Head-to-head trials are needed to verify the results of indirect analyses and provide additional guidance on optimal treatment choices.