January 29, 2011

Gastroenterology
Volume 140, Issue 2 , Pages 459-468.e1, February 2011

Patrick Marcellin, Xavier Forns, Tobias Goeser, Peter Ferenci, Frederik Nevens, Giampiero Carosi, Joost P. Drenth, Lawrence Serfaty, Koen De Backer, Rolf Van Heeswijk, Donghan Luo, Gaston Picchio, Maria Beumont

Abstract

Background & Aims
Recent studies have shown that 12 weeks of treatment with telaprevir, administered every 8 hours (q8h), combined with pegylated interferon (peginterferon) alfa-2a plus ribavirin significantly increased the rate of hepatitis C virus (HCV) eradication (sustained virologic response [SVR]) in patients infected with HCV genotype 1 compared with approved therapy. We investigated the efficacy, safety, tolerability, and pharmacokinetics of telaprevir given q8h or every 12 hours (q12h) in combination with peginterferon alfa-2a or alfa-2b.

Methods
Treatment-naive patients (n = 161) infected with HCV genotype 1 were randomly assigned to groups that were given open-label telaprevir (750 mg q8h or 1125 mg q12h) in combination with standard doses of peginterferon alfa-2a (180 μg/wk) and ribavirin (1000–1200 mg/day) or peginterferon alfa-2b (1.5 μg·kg−1·wk−1) and ribavirin (800–1200 mg/day). Patients received triple therapy for 12 weeks, followed by 12 or 36 additional weeks of treatment with peginterferon alfa and ribavirin, based on virologic response.

Results
Baseline characteristics were similar for all groups. SVR rates were 81.0% to 85.0% among groups; most patients received 24 weeks of therapy (68.0%). There were no significant differences in SVR rates (intent-to-treat analysis) among groups (P ≥ .787), between the pooled q8h and q12h groups (P = .997), or between the pooled peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin groups (P = .906). The safety profile was similar among all groups.

Conclusions
A high proportion (>80%) of patients achieved an SVR regardless of the telaprevir dosing frequency (q8h or q12h) or type of peginterferon alfa used (alfa-2a or alfa-2b).

Source
Gastroenterology
Volume 140, Issue 2 , Pages 450-458.e1, February 2011

Kathleen B. Schwarz, Regino P. Gonzalez–Peralta, Karen F. Murray, Jean P. Molleston, Barbara A. Haber, Maureen M. Jonas, Philip Rosenthal, Parvathi Mohan, William F. Balistreri, Michael R. Narkewicz, Lesley Smith, Steven J. Lobritto, Stephen Rossi, Alexandra Valsamakis, Zachary Goodman, Patricia R. Robuck, Bruce A. Barton, Peds-C Clinical Research Network

Abstract

Background & Aims
Although randomized trials of adults infected with hepatitis C virus (HCV) have shown that ribavirin increases the efficacy of pegylated interferon (PEG), such trials have not been performed in children. We conducted a randomized controlled trial of PEG and ribavirin, compared with PEG and placebo, in children 5 to 17 years old with chronic hepatitis C.

Methods
HCV RNA–positive children from 11 university medical centers were randomly assigned to receive either PEG alfa-2a (PEG-2a; 180 μg/1.73 m2 body surface area, subcutaneously each week; n = 55) and ribavirin (15 mg/kg orally in 2 doses daily) or PEG-2a and placebo (n = 59) for 48 weeks. The primary end point was sustained virologic response (SVR; lack of detectable HCV RNA at least 24 weeks after stopping therapy).

Results
SVR was achieved in 53% of children treated with PEG-2a and ribavirin, compared with 21% of children who received PEG-2a and placebo (P < .001). Early virologic response (HCV RNA reduction >2 log10 IU at 12 weeks) had a negative predictive value of only 0.89 in children with genotype 1, indicating that these children might benefit from 24 weeks of therapy before stopping treatment. Side effects, especially neutropenia, led to dose modification in 40% of children. Eighty-two percent of the PEG/ribavirin and 86% of the PEG/placebo group were in compliance with the year 2 follow-up visit; the durability of virologic response was 100% in both groups.

Conclusions
The combination of PEG and ribavirin is superior to PEG and placebo as therapy for chronic hepatitis C in children and adolescents.

Source