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.