Study: Twice Weekly Dose Better for Hep C

But Hepatitis Experts Remain Skeptical

From the WebMD Archives

July 30, 2003 -- New research suggests the best treatment for hepatitis C virus may be even more effective if given twice weekly rather than once a week, but experts contacted by WebMD say the study is far from convincing.

The approval of pegylated interferon two years ago represented a dramatic advance in the treatment of the hepatitis C virus. The new interferon works better than older versions of the drug and is given just once weekly.

Twice as Nice?

But the study by University of Vienna researchers calls into question the once-a-week dosing schedule. The investigation of 20 newly treated patients followed for one month found that those receiving twice-weekly injections of a standard dose of pegylated interferon had more continuous exposure to the drug and better early viral reductions than patients receiving the same dosage once a week.

Blood levels of the drug reached maximum levels 24 hours after injection, followed by an almost steady decline in the days that followed. By the end of the week, prior to the next dosing, no drug was detectable in the blood of nearly all of the patients treated with a once-weekly dose, but drug was detectable at all times in the patients given the drug on a twice-weekly schedule. Increases in amount of hepatitis C virus present in the blood corresponded to decreases in drug levels.

The study is published in the July issue of the Journal of Viral Hepatitis.

The study also showed that the level of the virus decreased in all patients within two days but increased again on day three. During the study, patients given the drug once a week continued to have increases in the level of the virus until the next treatment dose. In contrast, patients given the drug twice a week had a decrease in the levels of the hepatitis virus by the forth day because of the repeated treatment, and these levels remained low until the end of the study.

"At least during the initial phase of treatment, it appears that this drug needs to be given twice weekly to maintain constant viral suppression," study co-author Peter Ferenci tells WebMD. "This may translate into better sustained viral responses, but this has to be proven."


Experts Disagree

Hepatitis C treatment expert Bruce Bacon, MD, says the study has little clinical relevance precisely because the researchers did not look at whether the different dosing frequencies effectively clear the virus from blood and led to a sustained undetectable level of virus, which means the patient has cleared the virus and no longer has the infection. Bacon is director of the division of hepatology at Saint Louis University School of Medicine.

"These authors did not look at the only endpoint that matters," he tells WebMD. "If they were telling us that they had achieved a better sustained response with these patients, then that would be huge. But the patients were only followed for four weeks."

Most hepatitis C patients in the U.S. are treated for 48 weeks with a combination of pegylated interferon and the drug ribavirin. Seven years ago, only about 10% of patients achieved sustained responses. More than half of patients are cured today with the combination regimen.

Bacon says it is not clear if the response that was seen in the study within the early weeks of treatment is predictive of eventual viral clearance.

"Early response is of clinical interest, but it is of practical use only when there is an absence of response," he says. "That is why we do not continue treating patients who have not responded after 12 weeks of therapy."

Infectious disease specialist Margaret Koziel, MD, agrees that even if twice-weekly dosing does result in a better initial response to treatment, that is not necessarily predictive of a higher cure rate. She also expressed concerns about the greater potential for severe side effects with twice-weekly dosing. Koziel is an assistant professor of medicine at Harvard Medical School and a staff physician at Beth Israel Deaconess Medical Center.

Common side effects of interferon treatment include flu-like symptoms, fatigue, depression, and immune system suppression. The two treatment groups in this study had similar rates of these side effects, but Koziel says that does not mean they would continue to do so throughout treatment.

"Even if the dosage were the same, twice-weekly dosing could certainly have an impact on toxicity," she says. "These patients were not followed long enough to know."


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SOURCES: Journal of Viral Hepatitis, July, 2003. Peter Ferenci, professor, gastroenterology and hepatology, University of Vienna. Bruce Bacon, MD, director of the division of hepatology, St. Louis University School of Medicine. Margaret Koziel, MD, assistant professor of medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston.
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