Background: Up to 60% of patients with hepatitis C virus (HCV) genotype 1 infection do not have a sustained virologic response to therapy with peginterferon alfa plus ribavirin.
Methods: In this randomized, phase 3 trial, we evaluated the addition of telaprevir to peginterferon alfa-2a plus ribavirin in patients with HCV genotype 1 infection who had no response or a partial response to previous therapy or who had a relapse after an initial response. A total of 663 patients were assigned to one of three groups: the T12PR48 group, which received telaprevir for 12 weeks and peginterferon plus ribavirin for a total of 48 weeks; the lead-in T12PR48 group, which received 4 weeks of peginterferon plus ribavirin followed by 12 weeks of telaprevir and peginterferon plus ribavirin for a total of 48 weeks; and the control group (PR48), which received peginterferon plus ribavirin for 48 weeks. The primary end point was the rate of sustained virologic response, which was defined as undetectable HCV RNA 24 weeks after the last planned dose of a study drug.
Results: Rates of sustained virologic response were significantly higher in the two telaprevir groups than in the control group among patients who had a previous relapse (83% in the T12PR48 group, 88% in the lead-in T12PR48 group, and 24% in the PR48 group), a partial response (59%, 54%, and 15%, respectively), and no response (29%, 33%, and 5%, respectively) (P<0.001 for all comparisons). Grade 3 adverse events (mainly anemia, neutropenia, and leukopenia) were more frequent in the telaprevir groups than in the control group (37% vs. 22%).
Conclusions: Telaprevir combined with peginterferon plus ribavirin significantly improved rates of sustained virologic response in patients with previously treated HCV infection, regardless of whether there was a lead-in phase. (Funded by Tibotec and Vertex Pharmaceuticals; REALIZE ClinicalTrials.gov number, NCT00703118.).