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Baraclude Outperforms Epivir for Hepatitis B

Baraclude (entecavir) performed better than Epivir (lamivudine) in helping people with hepatitis B (HBV) to improve histologic and virologic measures and normalize liver-function, according to results from twin studies.

The studies were published in the New England Journal of Medicine and reported by MedPage Today on March 8, 2006.

The researchers conducted double-blind, randomized trials of Baraclude versus Epivir in people with HBV who had never received a nucleoside analog. The two studies differed by study population: one was e-antigen-negative, the other e-antigen-positive.

Results showed that people receiving Baraclude scored significantly higher in achieving primary and secondary endpoints in participants with both hepatitis B e-antigen-negative and e-antigen-positive infections.

After 48 weeks of treatment, 67% of participants with e-antigen-positive infections had undetectable serum HBV DNA levels, versus only 36% of participants on Epivir, reported Ting-Tsung Chang, MD, and colleagues of the National Cheng Kung University Medical College in Tainan, Taiwan, and colleagues elsewhere in Asia, Europe, North America and South America.

Similarly, at 48 weeks, 90% of participants with e-antigen-negative infections who were receiving Baraclude had no detectable HBV serum DNA levels, compared with 72% of participants on Epivir, according to Ching-Lung Lai, MD, of the Queen Mary Hospital in Hong King and colleagues elsewhere.

These studies show that HBV infection may not only be preventable through vaccination, but may be treated, wrote Jay H Hoofnagle, MD, of the National Institute of Diabetes and Digestive and Kidney Diseases, in an accompanying editorial.

"With its excellent potency and low rate of resistance, entecavir seems to be an outstanding agent for treating chronic hepatitis B," Dr Hoofnagle wrote. "Its use at present, however, should be tempered with the knowledge that this chronic liver disease is likely to require long-term therapy, and that this drug is easy to start but difficult to stop."

Clinical Trials

In the study of e-antigen-positive people, investigators randomly assigned 715 patients who had not previously received a nucleoside analogue to receive either Baraclude 0.5 mg or Epivir 100 mg once daily for at least 52 weeks.

The primary endpoint was specific histologic improvement at 48 weeks, and the secondary endpoints included a reduction in serum HBV DNA levels, loss of the hepatitis B e-antigen, seroconversion, and normalization of liver-function tests.

The results showed that, after 48 weeks, 226 of 314 participants receiving Baraclude (72%) had histologic improvement, compared with 195 of 314 (62%) of participants in the Epivir group.

In the trial by Dr Lai and colleagues, who examined the effects of the same two agents in e-antigen-negative patients, 648 patients who had never received nucleoside analogs were randomly assigned to receive Baraclude or Epivir at the same doses as in the first study.

The primary endpoint in this study was the same as in the study by Dr Change and colleagues.

In the second trial, at 48 weeks, 208 of 296 participants (70%) receiving Baraclude with baseline liver-biopsy specimens adequate for evaluation had histologic improvement, versus 174 of 287 participants (61%) receiving Epivir. Also, 90% of participants receiving Baraclude had undetectable serum HBV DNA levels, compared with 72% on Epivir.

Participants in both studies showed no evidence of resistance to Baraclude, and the safety and adverse-event profiles were similar between the two study-groups.

"Perhaps the most promising aspect of Baraclude therapy has been the low rate of antiviral resistance," Dr Hoofnagle wrote. "To date, resistance to entecavir [Baraclude] has been described only in patients with preexisting lamivudine [Epivir] resistance."

With regard to treatment, he wrote, "What, then, can be recommended? Primarily, therapy should be reserved for patients who need to be treated - those with active disease exemplified by raised serum alanine aminotransferase levels, by clinical or histologic evidence of progressive disease, or both.

"The oral antiviral agents are attractive because they are easy to administer, have minimal side effects, and are effective in the full spectrum of patients with chronic hepatitis B, including those with liver decompensation or other coexisting conditions," Dr. Hoofnagle wrote. "Either adefovir [Hepsera] or entecavir [Baraclude] is an appropriate first-line agent. Treatment probably should be continued indefinitely."

Dr Hoofnagle noted that careful monitoring may facilitate discontinuing treatment in patients who are e-antigen-negative or who convert to being negative while on therapy.

Posted: March 2006