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Pegylated interferons for the treatment of chronic hepatitis C: pharmacological and clinical differences between peginterferon-alpha-2a and peginterferon-alpha-2b
Chronic infection with hepatitis C virus (HCV) is a major healthcare problem, affecting an estimated 170 million people worldwide. Interferon-alpha has formed the basis of treatment regimens since the identification of HCV, either alone or in conjunction with the nucleoside analogue ribavirin. The r...
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Published in: | Drugs (New York, N.Y.) N.Y.), 2010, Vol.70 (2), p.147 |
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Main Author: | |
Format: | Article |
Language: | English |
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Online Access: | Get full text |
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Summary: | Chronic infection with hepatitis C virus (HCV) is a major healthcare problem, affecting an estimated 170 million people worldwide. Interferon-alpha has formed the basis of treatment regimens since the identification of HCV, either alone or in conjunction with the nucleoside analogue ribavirin. The relatively recent introduction of pegylated forms of interferon-alpha, with greater stability and in vivo activity, has substantially improved sustained virological response (SVR) rates compared with unmodified interferon-alpha, with SVR rates of 35-66% when used in conjunction with ribavirin in randomized controlled trials. Two pegylated interferon (peginterferon)-alpha molecules are commercially available for the treatment of chronic hepatitis C, and these differ in the size and nature of the covalently attached polyethylene glycol (PEG) moiety, with resulting differences in pharmacokinetics and in dosing regimens. Peginterferon-alpha-2b has a linear 12 kDa PEG chain covalently attached primarily to histidine-34 of interferon-alpha-2b via an unstable urethane bond that is subject to hydrolysis once injected, releasing native interferon-alpha-2b. The branched, 40 kDa PEG chain of peginterferon-alpha-2a is covalently attached via stable amide bonds to lysine residues of interferon-alpha-2a, and circulates as an intact molecule. Consequently, peginterferon-alpha-2a has a very restricted volume of distribution, longer half-life and reduced clearance compared with native interferon-alpha-2a, and can be given once weekly independently of bodyweight. Peginterferon-alpha-2b has a shorter half-life in serum than peginterferon-alpha-2a and requires bodyweight-based dosing. The majority of head-to-head randomized controlled trials, including the large, randomized IDEAL (Individualized Dosing Efficacy versus Flat Dosing to Assess Optimal Pegylated Interferon Therapy) trial (n = 3070), demonstrated similar SVR rates for peginterferon-alpha-2a and peginterferon-alpha-2b (41% vs 39% in IDEAL), in combination with ribavirin; however, two randomized controlled trials (n = 431 and 320) demonstrated a statistically significant benefit for peginterferon-alpha-2a (66% vs 54%, and 69% vs 54%). Furthermore, two large retrospective studies and one prospective observational study in real-life settings have shown a significant benefit for peginterferon-alpha-2a versus peginterferon-alpha-2b, although SVR rates were generally lower than those seen in controlled trials. The use of interfe |
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ISSN: | 1179-1950 |
DOI: | 10.2165/11531990-000000000-00000 |