title: Telaprevir: a review of its use in the management of genotype 1 chronic hepatitis C.
abstract: Telaprevir (Incivo®, Incivek®), an orally administered inhibitor of the hepatitis C virus non-structural protein NS3-4A serine protease, is used in combination with pegylated interferon (peginterferon)-alpha and ribavirin in the treatment of adults with genotype 1 chronic hepatitis C virus (HCV) infection (chronic hepatitis C). This article reviews data on the clinical efficacy and tolerability of telaprevir in adults with genotype 1 chronic hepatitis C and provides a summary of its pharmacological properties. In in vitro studies, telaprevir shows good activity against genotype 1 HCV, including viral isolates from patients with chronic hepatitis C. Numerous resistant variants of HCV have been identified in clinical isolates from patients receiving treatment with telaprevir-based therapy. However, the clinical relevance of viral variants emerging during treatment requires further study. Telaprevir administered for 12 weeks in combination with peginterferon-alpha-2a and ribavirin for up to 48 weeks was effective in the treatment of previously untreated or previously treated adults with genotype 1 chronic hepatitis C in three major randomized phase III trials. Sustained virological response rates (i.e. percentages of patients with undetectable HCV RNA levels 24 weeks after the last planned dose of study medication: the primary endpoint) achieved with the telaprevir-based regimens were significantly higher than those produced with peginterferon-alpha-2a and ribavirin alone (the 'current standard of care'). In the largest trial (the ADVANCE trial) in previously untreated patients, 24 weeks after the last planned dose of study drug, recipients of 12 weeks' treatment with telaprevir in combination with peginterferon-alpha-2a and ribavirin followed by treatment with peginterferon-alpha-2a and ribavirin for a further 12 or 36 weeks experienced significantly (p < 0.001) higher sustained virological response rates than patients who received peginterferon-alpha-2a and ribavirin dual therapy for 48 weeks (75% vs 44%). Adverse events were reported more frequently with telaprevir-based regimens than with peginterferon-alpha-2a and ribavirin dual therapy in the major trials. The most common adverse events included fatigue, rash, pruritus, anaemia and nausea. In conclusion, telaprevir in combination with peginterferon-alpha and ribavirin is an effective treatment for treatment-naive and previously treated adults with genotype 1 chronic hepatitis C - patient groups in whom peginterferon-alpha and ribavirin dual therapy may not be successful. Thus, telaprevir is a valuable new treatment option for use in combination with peginterferon-alpha and ribavirin in treatment-naive or previously treated adults with genotype 1 chronic hepatitis C.
authors.affiliation: Adis, Auckland, New Zealand. demail@adis.co.nz
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Perry
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012367:RNA, Viral / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011480:Protease Inhibitors; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a