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Differential antiviral effects of pegylated interferon-α2a and pegylated interferon-α2b in chronic hepatitis C

, : Differential antiviral effects of pegylated interferon-α2a and pegylated interferon-α2b in chronic hepatitis C. Clinical Drug Investigation 34(12): 871-878

Pegylated interferon (peg-IFN)-α2a and -α2b show different pharmacokinetic properties but are used interchangeably for hepatitis C treatment in traditional dual combinations and with newer agents. We assessed whether peg-IFN antiviral effects vary with peg-IFN subtype, affecting viral response in a differential manner. Chronic hepatitis C patients treated with ribavirin combined with peg-IFN-α2a (N = 109) or -α2b (N = 114) were studied. Hepatitis C virus RNA quantitation was performed by Cobas TaqMan 5 min before treatment start and subsequently after 48/72 h and 7, 14, 28 and 90 days. Antiviral effect was assessed in terms of viraemia changes over treatment. Histology grading and staging, interleukin-28B (IL28B) status and baseline viral genotype, alanine aminotransferase, gamma glutamyltransferase and glucose were analysed. Viraemia decline after 48/72 h and 7 days was significantly greater with peg-IFN-α2b (1.96 and 2.12 vs 1.49 and 1.20 log10 IU/mL with peg-IFN-α2a; p < 0.001). Differences were of larger extent in patients with advanced fibrosis (p = 0.002), genotype 1 infection (p = 0.002) and CT/TT genotypes of IL28B (p = 0.001). A rebound in viral load was observed significantly more often after the first dose in patients treated with peg-IFN-α2b (78 vs 28 % in those with peg-IFN-α2a; p = 0.0001). Differences between peg-IFNs disappeared by day 28 of treatment. There are significant pharmacodynamic differences between peg-IFN-α2a and -α2b in the early phase of chronic hepatitis C treatment. The greater early viral decline observed with peg-IFN-α2b was essentially confined to 'difficult to treat' patients. Whether this could affect response-guided treatment decision making, as well as triple drug regimens, needs to be assessed.


PMID: 25349040

DOI: 10.1007/s40261-014-0241-y

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