Pegylated Interferon-α2a and Ribavirin versus Pegylated Interferon-α2b and Ribavirin in Chronic Hepatitis C

Abstract

Results of trials and meta-analyses comparing pegylated interferon (PEG-IFN)-α2a and PEG-IFN-α2b for the treatment of chronic hepatitis C are conflicting. Our objective was to determine which PEG-IFN (α2a or α2b), in association with ribavirin, is the most effective for the treatment of chronic hepatitis C by performing an updated meta-analysis. MEDLINE (1950-2012) and EMBASE (1974-2012) databases, as well as the Cochrane Central Register of controlled trials and the Cochrane Database of Systematic Reviews, were searched. Reference lists of retrieved articles were scanned, and proceedings of major international conferences were manually searched for abstracts. Randomized clinical trials and non-randomized clinical studies comparing PEG-IFN-α2a with PEG-IFN-α2b in association with ribavirin in adult patients with chronic hepatitis C were included. Studies including HIV-positive patients or liver transplant recipients were excluded. The data extraction from each study was conducted independently by two authors, with disagreements resolved by consensus or by a third reviewer. The trial quality of randomized clinical trials was assessed by taking into account generation of allocation sequence, allocation concealment, efficacy of randomization, investigator blindness, description of withdrawals and dropouts and adherence to the intention-to-treat principle. Two meta-analyses were performed, the first including randomized clinical trials only, and the second including both randomized and non-randomized clinical studies. The primary outcome measure was frequency of sustained virological response (SVR). Heterogeneity and publication bias were systematically taken into account. This meta-analysis included 26 studies, 11 randomized and 15 non-randomized, with a total of 18,260 patients: 8,125 treated with PEG-IFN-α2a and 10,135 treated with PEG-IFN-α2b. In the meta-analysis that included randomized trials only, the SVR was significantly higher for patients treated with PEG-IFN-α2a than for those treated with PEG-IFN-α2b for genotypes 1 and 4 [odds ratio (OR) 1.45; 95 % CI 1.09-2.06; p = 0.013] and for all genotypes (OR 1.34; 95 % CI 1.05-1.72; p = 0.02). In the meta-analysis including both randomized and non-randomized studies, the SVR was significantly higher for PEG-IFN-α2a than for PEG-IFN-α2b for all genotypes (OR 1.24; 95 % CI 1.10-1.40; p < 0.001) and for genotypes 1 and 4 (OR 1.25; 95 % CI 1.14-1.36; p < 0.001); for genotypes 2 and 3, the SVR was greater for treatment with PEG-IFN-α2a than with PEG-IFN-α2b, with the difference tending towards significance (OR 1.15; 95 % CI 0.98-1.35; p = 0.08). A certain degree of heterogeneity was present amongst the various studies included in this meta-analysis. Publication bias was detected (particularly for analyses including only randomized controlled trials) and taken into account using appropriate statistical methods. Current evidence suggests that PEG-IFN-α2a and ribavirin is associated with a higher SVR than PEG-IFN-α2b and ribavirin in patients mono-infected with hepatitis C, particularly for genotypes 1 and 4.