Sixteen RCTs were included (n=5,080). Sample size ranged from 21 to 1,530. Eight studies reported adequate methods of randomisation, six described adequate allocation concealment, two reported blinding of outcome assessors and 14 reported intention-to-treat analysis.
Direct meta-analyses:
Dual therapy with pegylated interferon alfa-2a was associated with a statistically significant increase in sustained virological response compared to non-pegylated alfa-2a or -2b (RR 2.03, 95% CI 1.36 to 3.03; six studies). Heterogeneity was high (I2=86%). There was no statistically significant difference between non-pegylated alfa-2a regimes and pegylated interferon alfa-2a regimens (five studies, n=1,157) or alfa-2b regimens (one study, n=897).
Dual therapy with pegylated interferon alfa-2b was associated with a statistically significant increase in sustained virological response compared to non-pegylated alfa-2b (RR 1.28, 95% CI 1.11 to 1.48; 10 studies). Heterogeneity was moderate (I2=39%).
Withdrawal/treatment discontinuation rates ranged from 6% to 16% with pegylated interferon therapy. There were no statistically significant differences in rates of withdrawal or treatment discontinuation between non-pegylated interferon regimes and either pegylated alfa-2a regimens (five studies) or alfa-2b regimens (seven studies).
L’Abbe plots did not suggest any outliers or any influence on treatment effect of sustained virological response rates in the control group. Funnel plots and Egger’s test showed no evidence of publication bias for pegylated interferon alfa-2a, but there was evidence of publication bias for pegylated alfa-2b (p for Egger’s test 0.018). There were no significant differences in sustained virological response rates when studies were stratified by quality items.
Indirect meta-analysis:
There were no significant differences among studies in sustained virological response rates for groups treated with non-pegylated interferon.
There was no significant difference in sustained virological response between pegylated interferon alfa-2a and pegylated alfa-2b regimens (RR 1.59, 95% CI 0.07 to 4.46). Confidence intervals were wide.
Subgroup analysis:
Results were similar when only studies that compared pegylated interferon with no pegylated alfa-2b were analysed and when studies were stratified by HIV status, hepatitis C virus genotype, higher doses of ribavirin, use of FDA-approved dose of pegylated interferon, amantadine co-therapy and using the trim-and fill method to account for publication bias.
Using indirect meta-analyses, there were no significant differences between pegylated alfa-2a and alfa-2b in adverse events, anaemia, neutropenia, depression or flu-like symptoms.
Results for further subgroup analyses were reported.