Two new randomized controlled trials show that treating Hepatitis C (HCV) with peginterferon and ribavirin for shorter durations can yield success rates similar to those from longer treatment lengths, with cost-savings and lower risk of serious side effects. Patients’ HCV-RNA levels after 4 weeks of treatment may be an important factor for determining the best treatment length. These findings are in the January issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The articles are also available online at Wiley Interscience at (http://www.interscience.wiley.com/journal/hepatology).
HCV genotype is the single most important predictor of a patient’s outcome after treatment with peginterferon and ribavirin. Only about half of all patients with genotype 1 will achieve a sustained viral response, compared to 70 to 90 percent of patients with genotype 2 or 3. Regardless of HCV genotype, patients who respond quickly to the drugs are also more likely to be cured by them. Based on these differences, and because the therapy is costly and carries risks of serious side effects, researchers have been exploring ways to customize treatment for each patient.
Researchers led by Alessandra Mangia of Italy’s Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo Della Sofferenza, in San Giovanni Rotondo conducted a randomized controlled trial of patients with HCV genotype 1. They hypothesized that variable treatment duration based on the first measurement of undetectable HCV RNA would be as effective as standard 48-week treatment. They enrolled 696 patients, 237 of whom received standard HCV. The remaining 459 were treated for 24, 48, or 72 weeks, if HCV-RNA was undetectable at 4, 8, or 12 weeks, respectively.
Nearly 49 percent of patients receiving variable treatment based on detectable viral levels achieved a sustained viral response, compared to 45 percent of patients in the standard group. A majority of patients who showed a viral response at week 4 were cured by a 24-week therapy. However, for patients who did not show a response until week 12, 72 weeks of treatment was required for an approximately similar cure rate.
“In conclusion,” the authors report, “variable treatment duration ensures a sustained viral response rate similar to that of standard treatment duration, with potential significant reduction in cost and side effects.”
Meanwhile, researchers in Norway led by Olav Dalgard conducted a randomized controlled trial of 428 patients with HCV genotype 2 or 3 to assess the success rate of 14 weeks of treatment with peginterferon plus ribavirin. Patients who achieved a viral response after 4 weeks were randomly assigned to complete either 14 or 24 total weeks of treatment.
They found that 81 percent of patients in the 14-week treatment group achieved a sustained viral response, with 86 percent still cured at 24-weeks post-treatment. Nearly 91 percent of patients in the 24-week treatment group achieved a sustained viral response, with 93 percent still cured at 24-weeks post-treatment.
“We cannot formally claim that 14 weeks treatment is non-inferior to 24 weeks treatment,” the authors conclude, “However, the sustained viral response rate after 14 weeks treatment is high, and although longer treatment may give a slightly better sustained viral response rate, we believe considerable economical savings, good response to re-treatment and less side effects make it rational to treat patients with genotype 2 or 3 and rapid viral response for only 14 weeks.”
Both studies agree that customizing treatment lengths based on the patient response to therapy could lead to very good outcomes, with fewer harmful side effects, and lower costs.
Article: “Individualized Treatment Duration for Hepatitis C Genotype 1 Patients: A Randomized Controlled Trial.” Mangia, Alessandra; Minerva, Nicola; Bacco, Donato; Cozzolongo, Raffaele; Ricci, Giovanni; Carretta, Vito; Vinelli, Francesco; Scotto, Gaetano; Montalto, Giuseppe; Romano, Mario; Cristofaro, Giuseppe; Mottala, Leonardo; Spirito, Fulvio; Andriulli, Angelo. Hepatology; January 2008.
Article: “A Randomized Controlled Trial of Pegylated Interferon Alfa and Ribavirin for 14 vs. 24 Weeks in Patients with HCV Genotype 2 or 3 and Rapid Virological Response.” Dalgard, Olav; Bjoro, Kristian; Ring-Larsen, Helmer; Bjornsson, Einar; Holberg-Petersen, Mona; Skovlund, Eva; Reichard, Olle; Bo, Sundelof; Myrvang, Bjorn; Ritland, Stale; Aril, Fryden; Hellum, Kjell; Florholmen, Jon; Verbaan, Hans. Hepatology; January 2008.
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Hepatology