Clinical

Response to hepatitis C treatment evident within weeks

Last Updated: 2009-07-22 17:00:27 -0400 (Reuters Health)

By Karla Gale

NEW YORK (Reuters Health) - Two standard treatments for hepatitis C virus (HCV) infection - ribavirin plus either peginterferon alfa-2b or peginterferon alfa-2a - are equally effective and have similar side effect profiles, according to a report published Online First by The New England Journal of Medicine on July 22. Findings from the prospective clinical trial also indicate that a sustained virologic response could be predicted by week 4.

"The biggest 'surprise finding,'" lead author Dr. John G. McHutchison told Reuters Health, "was that patients who developed anemia due to the ribavirin had higher response rates. This likely reflects that the anemia is indicative of more ribavirin getting into cells where it works (including red cells). Thus, the anemia is a pharmacodynamic marker of ribavirin."

The Individualized Dosing Efficacy vs. Flat Dosing to Assess Optimal Pegylated Interferon Therapy (IDEAL) study included 3070 treatment-na�ve adult patients with compensated liver disease due to chronic HCV infection and a detectable plasma HCV RNA level.

Patients were randomly assigned to peginterferon alfa 2b (Pegintron, Schering-Plough) at the standard dose of 1.5 �g/kg/wk, or at a lower dose of 1.0 �g/kg per week, plus ribavirin at a dose of 800 to 1400 mg/d, based on body weight. The third treatment group received peginterferon 2a (Pegasys, Roche) 180 �g/wk plus ribavirin 1000-1200 mg/d.

The treatment period was 48 weeks, with the primary end point defined as an undetectable HCV RNA levels 24 weeks after completing therapy.

Response rates did not differ significantly among the three treatment groups: 39.8% for standard-dose peginterferon alfa-2b, 38.0% for low-dose peginterferon alfa-2b, and 40.9% for peginterferon alfa-2a.

"In all three groups," Dr. McHutchison, from Duke University in Durham, North Carolina, and his associates report, "HCV RNA suppression at treatment weeks 4 and 12 was strongly associated with achievement of sustained virologic response."

Specifically, among patients with undetectable HCV RNA levels at weeks 4 and 12, more than three quarters achieved a sustained virologic response.

The authors note that, despite the similarities, patients treated with peginterferon alfa-2a were more likely to respond to treatment, but they were also more likely suffer relapse after completing the regimen. On the other hand, more patients treated with peginterferon alfa-2b dropped out at week 12 or 24 because of an insufficient virologic response.

The research team also notes that the rate of sustained virologic response was higher among patients whose hemoglobin level dipped to below 10 g/dL during treatment and required a dose reduction in ribavirin. Lowering the dose of ribavirin did not appear to affect the probability of sustained virologic response.

In general, the side effect profiles and tolerability of the regimens were the same, Dr. Hutchinson said.

"The clinical implications are that, overall, both treatment strategies are equivalent in terms of cure rates," he added. "Predicting who will respond and measuring the viral levels at week 4 are definitely important, and our data solidify that for clinical practice."

"I think the important thing to potentially highlight is that these data now indicate that we have two equivalent backbones of therapy with pegIFN and ribavirin on which to build our future therapies, which will include direct anti-virals such as protease inhibitors."

The report is slated for print publication in the August 6 print version of The New England Journal of Medicine. The study was sponsored by the Schering-Plough Corporation

N Engl J Med 2009;361:580-593.