Drug & Device Development

Peginterferon clears hepatitis D virus in nearly one quarter of cases

Last Updated: 2011-01-26 17:10:24 -0400 (Reuters Health)

By Gene Emery

BOSTON (Reuters Health) - Forty eight weeks of treatment with peginterferon alfa-2a cleared hepatitis D virus (HDV) in nearly one quarter of patients, according to a study in the January 27 New England Journal of Medicine.

There is currently no approved therapy for HDV.

Dr. Michael Manns of Hannover Medical School in Germany and his colleagues also gave adefovir to some of the 90 volunteers to test its effectiveness, but found that it produced no improvement unless it was combined with peginterferon.

"This is the largest prospective study of peginterferon so far and it shows you can (have) active clearance of hepatitis delta virus," he told Reuters Health in a telephone interview. "It's also interesting that two of the 29 patients lost surface antigen, which is the closest you can get to a cure in hepatitis D."

F. Hoffmann-La Roche and Gilead Sciences paid for the study.

Hepatitis D is present in about 10% of people infected with hepatitis B virus and can lead to fulminant acute hepatitis, severe chronic hepatitis, cirrhosis and hepatocellular carcinoma.

Until now "there have been no impressive therapies for hepatitis D virus because you have a disease with two viruses which runs a more aggressive course, so this is a very difficult-to-treat population," Dr. Manns said.

As part of the study, 31 volunteers were given 180 micrograms of peginterferon alfa-2a per week combined with 10 mg of adefovir daily; 29 received peginterferon plus placebo and the remaining 30 received adefovir and placebo.

The primary end point was normalization of alanine aminotransferase levels and clearance of HDV RNA at week 48.

After 48 weeks, the test for HDV was negative in 23% of those who received both drugs, 24% of patients who got the long-acting interferon alone and 0% when the treatment consisted only of adefovir (P=0.004 for the single-drug treatments).

Two people in both peginterferon groups had normal levels of alanine aminotransferase.

Twenty four weeks after the drugs were stopped, 28% who received peginterferon alone had no trace of HDV RNA, although one patient had suffered a relapse with the reappearance of HDV RNA. None of the adefovir patients showed such improvement.

Side effects were more common in the peginterferon group -- 81% who received just that drug reported them compared to 60% of the adefovir recipients. The most common side effects -- fatigue, headache, abdominal pain, rash or myalgia -- were reported by at least 7 of the patients in both groups. Those were also some of the most common adverse effects in the adefovir group, but they were seen at lower levels.

However, serious side effects were more frequent among those taking adefovir (20%) versus interferon (6%).

"Further studies are needed to determine whether patients with a slow response to treatment who have clinically significant declines in HDV RNA levels during treatment without becoming HDV RNA-negative would benefit from a longer period of treatment," the researchers said.

Dr. Manns said a study is already underway to combine peginterferon with the anti-HIV drug tenofovir for 96 weeks.

SOURCE: http://bit.ly/e2tE7u

N Engl J Med 2011.