Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection
John G McHutchison, Gregory T Everson, Stuart C Gordon, Ira M Jacobson, Mark Sulkowski, Robert Kauffman, Lindsay McNair, John Alam, Andrew J Muir, PROVE1 Study Team, N Afdhal, S Arora, V Balan, H Vargas, D Bernstein, M Black, R Brown, N Bzowej, G Davis, A Di Bisceglie, J Dienstag, G Everson, S Faruqui, J Franco, M Fried, R Ghalib, S C Gordon, J Gross, I M Jacobson, D Jensen, M Kugelmas, P Kwo, E Lawitz, W Lee, P Martin, D Nelson, P Northup, K Patel, F Poordad, R K Reddy, M Rodriguez-Torres, V Rustgi, E Schiff, K Sherman, M Shiffman, M Sulkowski, G Szabol, Z Younossi, John G McHutchison, Gregory T Everson, Stuart C Gordon, Ira M Jacobson, Mark Sulkowski, Robert Kauffman, Lindsay McNair, John Alam, Andrew J Muir, PROVE1 Study Team, N Afdhal, S Arora, V Balan, H Vargas, D Bernstein, M Black, R Brown, N Bzowej, G Davis, A Di Bisceglie, J Dienstag, G Everson, S Faruqui, J Franco, M Fried, R Ghalib, S C Gordon, J Gross, I M Jacobson, D Jensen, M Kugelmas, P Kwo, E Lawitz, W Lee, P Martin, D Nelson, P Northup, K Patel, F Poordad, R K Reddy, M Rodriguez-Torres, V Rustgi, E Schiff, K Sherman, M Shiffman, M Sulkowski, G Szabol, Z Younossi
Abstract
Background: Current therapy for chronic hepatitis C virus (HCV) infection is effective in less than 50% of patients infected with HCV genotype 1. Telaprevir, a protease inhibitor specific to the HCV nonstructural 3/4A serine protease, rapidly reduced HCV RNA levels in early studies.
Methods: We randomly assigned patients infected with HCV genotype 1 to one of three telaprevir groups or to the control group. The control group (called the PR48 group) received peginterferon alfa-2a (180 microg per week) and ribavirin (1000 or 1200 mg per day, according to body weight) for 48 weeks, plus telaprevir-matched placebo for the first 12 weeks (75 patients). The telaprevir groups received telaprevir (1250 mg on day 1 and 750 mg every 8 hours thereafter) for 12 weeks, as well as peginterferon alfa-2a and ribavirin (at the same doses as in the PR48 group) for the same 12 weeks (the T12PR12 group, 17 patients) or for a total of 24 weeks (the T12PR24 group, 79 patients) or 48 weeks (the T12PR48 group, 79 patients). The primary outcome was a sustained virologic response (an undetectable HCV RNA level 24 weeks after the end of therapy).
Results: The rate of sustained virologic response was 41% (31 of 75 patients) in the PR48 group, as compared with 61% (48 of 79 patients) in the T12PR24 group (P=0.02), 67% (53 of 79 patients) in the T12PR48 group (P=0.002), and 35% (6 of 17 patients) in the T12PR12 group (this group was exploratory and not compared with the control group). Viral breakthrough occurred in 7% of patients receiving telaprevir. The rate of discontinuation because of adverse events was higher in the three telaprevir-based groups (21%, vs. 11% in the PR48 group), with rash the most common reason for discontinuation.
Conclusions: Treatment with a telaprevir-based regimen significantly improved sustained virologic response rates in patients with genotype 1 HCV, albeit with higher rates of discontinuation because of adverse events. (ClinicalTrials.gov number, NCT00336479.)
2009 Massachusetts Medical Society
Source: PubMed