Higher Doses of Pegylated Interferon and Ribavirin May Increase Sustained Respon

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Higher Doses of Pegylated Interferon and Ribavirin May Increase Sustained Response Rates in Hard-to-Treat Patients with Chronic Hepatitis C

By Liz HighleymanMany individuals with chronic hepatitis C virus (HCV) infection treated with standard interferon-based therapy fail to achieve sustained virological response (SVR), or continued undetectable HCV viral load 6 months after completion of therapy. This is especially the case for "hard to treat" patients, such as those with HCV genotype 1, high viral load, or obesity.In an effort to improve response, researchers have explored alternative regimens, including longer treatment durations and higher drug doses. As reported in the October 2008 issue of Hepatology, Fried of the University of North Carolina at Chapel Hill and colleagues compared the efficacy of standard-dose and high-dose regimens of pegylated interferon alfa-2a (Pegasys) plus ribavirin.This double-blind study included previously untreated adults with HCV genotype 1, baseline HCV RNA levels greater than > 800,000 IU/mL, and body weight > 85 kg. Participants were randomly assigned to receive pegylated interferon at doses of either 180 or 270 mcg/week plus either 1200 or 1600 mg/day ribavirin for 48 weeks (4 combination regimens were evaluated). The primary endpoint was HCV viral kinetics during the first 24 weeks of therapy. Result

• Patients receiving the high 270 mcg/week pegylated interferon dose experienced a significantly greater reduction in HCV RNA than those receiving the standard 180 mcg/week dose in combination with 1600 mg/day ribavirin (P = 0.04).• The reduction in HCV RNA was also greater with the high pegylated interferon dose combined with 1200 mg/day ribavirin (P = 0.06). • Patients randomized to the higher doses of both pegylated interferon and ribavirin experienced the highest rate of sustained virological response, at 47%.• This group also had the lowest relapse rate, at 19%.• However, the regimen containing high doses of both drugs was less well-tolerated than the others.

Based on these findings, the study authors concluded, "Higher fixed doses of [pegylated interferon] alfa-2a (270 mcg/week) and ribavirin (1600 mg/day) may increase sustained virologic response rates compared with lower doses of both drugs in patients with a cluster of difficult-to-treat characteristics."University of North Carolina, Chapel Hill, NC; University of Chicago, Chicago, IL; Fundacion de Investigacion de Diego Santurce, San , Puerto Rico; Kaiser Permanente Medical Center, San Diego, CA; St. Louis University, St. Louis, MO; Veterans Affairs Medical Center, Long Beach, CA; Scripps Clinic, La Jolla CA; Roche, Nutley, NJ; University of Florida, Gainesville, FL.