LOS ANGELES — Extended combination therapy with consensus interferon for 72 weeks appears to help improve the viral response of patients with chronic hepatitis C virus who have previously relapsed after a 48-week course of treatment, according to a study presented at the annual Digestive Disease Week.
The investigator-initiated study, conducted by researchers from the University of Tübingen in Germany, showed that at the end of 72 weeks of daily therapy, the majority of patients treated with a combination of either consensus interferon plus ribavirin or pegylated interferon alfa-2a plus ribavirin had a reduction in hepatitis RNA. However, the drop was not statistically significant, said the lead study author, Dr. Stephan Kaiser, a professor of medicine at the university.
The investigators compared the two interferon combinations in 81 patients who had experienced a previous relapse after a standard 48 weeks of pegylated interferon plus ribavirin. At the end of week 72, 89% of patients taking the consensus interferon combination were in remission, compared with 76% of the pegylated alfa-2a interferon group.
But relapse rates remained high in the study, Dr. Kaiser said. The pegylated alfa-2a interferon combination led to significantly higher rates of relapse than the consensus interferon combination. About 44% of the patients in the pegylated alfa-2a interferon combination group had a sustained viral response after completing treatment, compared with 69% of those in the consensus interferon group.
Overall, the study indicated that treatment for relapse can be successful using consensus therapy for an extended period, but more research is needed in multicenter trials, Dr. Kaiser said.
Researchers also presented new data on treatments for another difficult-to-treat population: nonresponders. Interim results from an ongoing phase II multicenter trial show that a combination of valopicitabine (NM283) at high doses plus pegylated interferon can reduce hepatitis RNA at 24 weeks of treatment, reported Dr. Paul Pockros of Scripps Clinic in California and his colleagues.
The five-arm study is comparing valopicitabine alone with three different doses of valopicitabine (400 mg/day, 800 mg/day, and dose-ramping from 400 to 800 mg/day) in combination with pegylated interferon, and with pegylated interferon plus ribavirin as a control.
Valopicitabine, manufactured by Idenix Pharmaceuticals, is the first nucleotide-type HCV polymerase inhibitor to advance to phase II trials. The study is funded by the drug maker.
The best results—about a 3-log decrease in hepatitis RNA—were achieved with the 800-mg dose of valopicitabine plus pegylated interferon. However, some patients experienced vomiting and nausea at initiation of treatment, and three patients were hospitalized with dehydration, so researchers stopped using the 800-mg dose and are continuing with 200-mg and 400-mg doses of the drug.
The results with the combination of 400 mg of valopicitabine and pegylated interferon were less promising in the nonresponder study population, with about a 2.5-log decrease, Dr. Pockros said.
Continued treatment is needed to find out if there will be a sustained response with the new drug combination, Dr. Pockros said, and to find out if the drug will be more effective for preventing relapse than are current therapies.