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Pegylated interferons α2a and α2b in the treatment of chronic hepatitis C

Nature Reviews Gastroenterology & Hepatology volume 7, pages 485–494 (2010)Cite this article

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Abstract

Chronic infection with HCV has an estimated prevalence of 1.6–2.0% worldwide and is a major cause of liver-related death. The first attempts to halt the progression of infection relied on the empirical use of interferon (IFN), a naturally occurring cytokine that is implicated in antiviral innate immunity. The first studies of this treatment in the early 1990s, however, led to disappointing response rates. These response rates subsequently improved with the empirical addition of the guanosine analog ribavirin to the treatment regimen. To improve the effectiveness and tolerability of the three times per week therapeutic schedule of IFN, two forms of pegylated interferon (PEG-IFN) were developed in the early 2000s—PEG-IFN-α2a and PEG-IFN-α2b. These two compounds differ markedly in size, structure, site of attachment of the polyethylene glycol moiety and type of bond involved in pegylation, which ultimately confer different pharmacokinetics and biological activity. Unsurprisingly, researchers question whether the two PEG-IFNs also differ in clinical effectiveness, but the re-analysis of restrospective studies and the results of three head-to-head studies have left this issue open. We have, therefore, scrutinized the design and conduct of all available studies to unravel the reasons behind the therapeutic differences between PEG-IFN-α2a and PEG-IFN-α2b.

Key Points

  • Pegylated interferons (PEG-IFNs) α2a and α2b differ considerably in terms of their pharmacokinetics and biological activity as a direct consequence of their different pegylation characteristics

  • PEG-IFN-α2a or PEG-IFN-α2b, in combination with ribavirin, are both approved for the treatment of chronic hepatitis C

  • Direct comparisons of the two PEG-IFN regimens are difficult because of their different dosing, and the different ribavirin doses and dose-reduction strategies used

  • The PEG-IFN-α2a regimen had higher response rates than the PEG-IFN-α2b regimen in two head-to-head, randomized studies, and a meta-analysis of 13 studies in patients with chronic hepatitis C

  • Further studies are needed to assess whether the outcomes of patients treated with the two therapeutic regimens are differentially influenced by host and viral factors

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Figure 1: The JAK–STAT interferon signaling pathway.
Figure 2: Response rates for the efficacy of pegylated interferons.

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Authors and Affiliations

  1. First Division of Gastroenterology, A. M. Migliavacca Center for Liver Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via F. Sforza 35, Milan, 20122, Italy

    Alessio Aghemo & Massimo Colombo

  2. Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Via San Vittore 12, Milan, 20122, Italy

    Maria Grazia Rumi

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  1. Alessio Aghemo
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  2. Maria Grazia Rumi
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Contributions

A. Aghemo and M. G. Rumi contributed equally to researching the data for the article. A. Aghemo, M. G. Rumi and M. Colombo contributed equally to substantial discussions of the content, to writing the article and to reviewing and/or editing the manuscript before submission.

Corresponding author

Correspondence to Massimo Colombo.

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Competing interests

M. G. Rumi declares that she has a speaking and teaching role with Roche.

M. Colombo declares that he has received grant and research support from Schering-Plough, Roche, Novartis and Bristol-Myers Squibb, he is on the advisory committees for Schering-Plough, Roche, Novartis, Vertex, Bristol-Myers Squibb, Gilead Sciences and Bayer and he has speaking and teaching roles with Schering-Plough, Roche, Novartis, Vertex, Gilead Sciences, Bristol-Myers Squibb and Bayer.

A. Aghemo delcares no competing interests.

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Aghemo, A., Rumi, M. & Colombo, M. Pegylated interferons α2a and α2b in the treatment of chronic hepatitis C. Nat Rev Gastroenterol Hepatol 7, 485–494 (2010). https://doi.org/10.1038/nrgastro.2010.101

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