Telaprevir user's guide.
Telaprevir is a potent HCV NS3/4A protease inhibitor. A completed development program has demonstrated the superior efficacy of a regimen of telaprevir combined with pegylated interferon alfa and ribavirin (PR) over PR alone in patients with HCV genotype 1. In the ADVANCE trial in treatment-naïve patients, 12 weeks of telaprevir, peginterferon alfa-2a and ribavirin followed by either 12 or 36 weeks of PR alone (depending upon extended rapid virologic response, or eRVR, i.e. HCV RNA undetectability at weeks 4 and 12), was associated with sustained virological response (SVR) in 75% of patients compared with 46% receiving PR for 48 weeks. The ILLUMINATE trial established the foundation for response-guided therapy in patients with eRVR. The REALIZE trial in treatment-experienced patients showed a gradient of SVR from prior relapsers (86%) to partial responders (57%) to null responders (31%), with rates of virologic failure and emergent resistance highest in the latter group. Incremental adverse effects of telaprevir include rash, anemia, pruritus, diarrhea, and nausea. Treatment naïve patients and relapsers are eligible for response-guided therapy. Stopping rules of telaprevir-based treatment include HCV RNA > 1000 IU/ml at weeks 4 and 12.
Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY 10021, USA.
Ann Marie
AM
Liapakis
Ira
I
Jacobson
D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004351:Drug Resistance / Q000187:drug effects; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a