Pegylated Interferon alfa-2a (Pegasys) Relapse Rates in Genotype 1 Chronic Hepatitis C Patients Depend on Weight-based Ribavirin Dosage

Standard therapy for chronic hepatitis C virus (HCV) infection consists of pegylated interferon alfa-2a (Pegasys) or pegylated interferon alfa-2b (PegIntron) plus weight-adjusted ribavirin. An adequate cumulative dosage of ribavirin per kilogram of body weight helps prevent HCV relapse and therefore is a significant predictor of sustained virological response (SVR).

A comparison of PegIntron/ribavirin versus Pegasys/ribavirin in the IDEAL trial indicated that SVR rates were similar, but the likelihood of relapse was significantly lower in the PegIntron arm. Some experts expressed skepticism about these findings since the ribavirin regimens used were not the same in both treatment arms (both were administered according to their package insert dosing instructions at the time).

Following up on these findings, German researchers performed a retrospective analysis to evaluate whether ribavirin dose might explain these findings. Results were published in the April 2009 issue of Scandanavian Journal of Gastroenterology.

As background, they noted that in the IDEAL trial, patients weighing > 105 kg reach a maximum ribavirin dose of 13.2 mg/kg ribavirin in the PegIntron arm regimen compared with 11.3 mg/kg in the Pegasys arm.

The present analysis aimed to determine relapse rates in genotype 1 chronic hepatitis C patients treated with pegylated interferon alfa-2a in relation to weight-based ribavirin dose.

The analysis included 98 patients, all of whom completed treatment with pegylated interferon alfa-2a plus weight-based ribavirin -- 1000 mg/day for patients weighing < 75 kg or 1200 mg/day for those weighing > 75 kg -- for 48 weeks. A low ribavirin dose was defined as < 13.2 mg/kg body weight. Patients with a ribavirin dose > 13.2 mg/kg were compared with those with a dose < 13.2 mg/kg.

Results

The 84 patients with a ribavirin dose > 13.2 mg/kg (n=84) had a relapse rate of 19.0%, in contrast to 71.4% for the 14 patients with a ribavirin dose < 13.2 mg/kg (P = 0.0013).

The SVR rate was significantly higher in the > 13.2 mg/kg ribavirin dose group compared with the < 13.2 mg/kg group (59.5% vs 28.6%, respectively).

Based on these findings, the authors concluded, "Weight-adapted ribavirin dosing in combination with [pegylated interferon alfa-2a] to avoid giving low doses of ribavirin should be evaluated. This will minimize relapse, especially in HCV genotype 1 patients."

Medical Department, Hepatology and Gastroenterology, Friedrich-Alexander University of Erlangen, Germany.

April 2009