Telaprevir

The standard treatment for genotype 1 chronic hepatitis C consists of the peginterferon alfa + ribavirin combination taken for 24 to 48 weeks. When added to this combination, boceprevir, an inhibitor of hepatitis C virus (HCV) NS3/4A serine protease, increases virological efficacy at a cost of generally acceptable adverse effects (mainly anaemia). However, more trials are needed to assess its impact on morbidity and mortality. Telaprevir was authorised in the European Union soon after boceprevir, also as an adjunct to standard therapy. A double-blind randomised trial in 1088 previously untreated patients showed that adding telaprevir to the peginterferon alfa-2a + ribavirin combination, as compared with adding placebo, led to a significantly higher rate of sustained virological response (about 79% versus 46%). In another randomised but unblinded trial in 540 patients, the rates of sustained virological response did not differ whether patients who had an early virological response were treated for 24 or 48 weeks. A double-blind randomised trial including 662 patients in whom initial treatment with peginterferon alfa-2a + ribavirin had failed showed that further treatment with the standard regimen plus telaprevir resulted in a significantly higher rate of sustained virological response compared to adding placebo, regardless of the type of failure (relapse: 86% versus 22%; partial response: 59% versus 15%; nonresponse: 32% versus 5%). There are no head-to-head comparisons between telaprevir and boceprevir. No firm conclusions on respective efficacy can be drawn from an indirect comparison of the data. The most common adverse effects associated with the addition of telaprevir, as compared to adding placebo, were rash (55.2% versus 32.7%), anaemia (32.1% versus 14.8%), and anorectal disorders (26% versus 5%). Severe rash occurred in 0.4% of patients receiving telaprevir, and severe anaemia in 4.9%. Telaprevir is metabolised by and inhibits cytochrome P450 isoenzyme CYP 3A4. Telaprevir is also a P-glycoprotein substrate, resulting in a high risk of pharmacokinetic interactions. The adverse effects of telaprevir are more difficult to manage than those of boceprevir. This means that telaprevir should be reserved for patients in whom boceprevir fails, at least until the respective long-term effects of the two drugs are better documented.