Long-term Entecavir (Baraclude) Produces Sustained Viral Suppression with Little Resistance in HBeAg Positive Chronic Hepatitis B Patients

		SUMMARY: Extended treatment with the nucleoside analog entecavir (Baraclude) for 5 years maintained or increased rates of HBV viral load suppression and ALT normalization seen after initial shorter duration therapy in hepatitis B "e" antigen (HBeAg) positive patients, according to a report in the January 4, 2010 advance online edition of Hepatology. Additional patients achieved HBeAg loss and seroconversion, entecavir remained well tolerated, and only 1 person developed resistance.

By Liz Highleyman

Entecavir has demonstrated potent antiviral activity and produced favorable outcomes during an initial treatment period of 48 weeks. But patients may relapse after discontinuing therapy, suggesting that longer treatment duration may be beneficial. Prolonged treatment may increase the risk of resistance, however, which has proven to be a barrier to long-term treatment with lamivudine (Epivir-HBV), an older HBV drug.

In the present study, Ting-Tsung Chang from National Cheng Kung University in Taiwan and an international team of colleagues assessed extended entecavir treatment for up to 5 years.

The analysis included participants from study ETV-022, which previously demonstrated that 0.5 mg daily entecavir was superior to lamivudine at suppressing HBV DNA in previously untreated HBeAg positive chronic hepatitis B patients treated for 48 weeks. A subset of 183 participants treated with entecavir opted to enroll in an open-label extension study, ETV-901.

The entecavir long-term cohort consisted of 146 patients who received 0.5 mg daily entecavir for at least 1 year in ETV-022 and then -- with a gap of no more than 35 days -- took 0.1 mg daily entecavir in ETV-901 for up to 240 weeks. Some patients had a period of combination therapy with entecavir plus lamivudine. Most people who had already achieved HBeAg seroconversion did not enroll in the extension, so this cohort included a higher proportion of serological non-responders.

Results

	After 5 years on entecavir, 94% of long-term cohort participants had HBV DNA < 300 copies/mL.
	80% achieved normal alanine transaminase (ALT) levels.
	In addition to those patients who achieved serological responses during ETV-022, 23% achieved HBeAg seroconversion and 1.4% experienced hepatitis B surface antigen (HBsAg) loss during ETV-901.
	Over 5 years, entecavir resistance emerged in only 1 patient.
	A total of 47 patients discontinued treatment prior to 240 weeks.
	The safety profile of entecavir was consistent with findings at 48 weeks, with no unexpected adverse events.

In conclusion, the study authors wrote, "Extended therapy with entecavir through 5 years maintained or increased rates of HBV DNA suppression and ALT normalization. Additional patients also achieved HBeAg loss and seroconversion."

"Entecavir provides sustained viral suppression with minimal resistance during long-term treatment of HBeAg positive chronic hepatitis B," they added.

"The importance of maintaining prolonged HBV DNA suppression to avoid or minimize the long-term complications of chronic hepatitis B has been recognized in several long-term studies of disease progression and outcome," they noted in their discussion. "It has also been shown that even patients with low-level HBV DNA viremia (below 104 to 105 copies/mL) are at risk of fibrosis, cirrhosis, and hepatocellular carcinoma."

"Current chronic hepatitis B treatment recommendations advocate sustained suppression of HBV DNA as the primary goal of antiviral therapy," they continued. "The rate of entecavir resistance remains rare over long-term therapy and distinguishes it from other HBV antivirals with long-term data. Entecavir's resistance profile is believed to result from its potent viral suppression and high genetic barrier to resistance."

Medical College, National Cheng Kung University, Tainan, Taiwan, ROC; Queen Mary Hospital, Hong Kong, China; Kangnam St. Mary Hospital, The Catholic University of Korea, Seoul, Korea; Foothills Provincial General Hospital, University of Calgary, Calgary, Canada; Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, SP, Brazil; Department of Hepatology and Liver Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA; Department of Infectious Diseases and Hepatology, Nicolaus Copernicus University, Bydgoszcz, Poland; Department of Hepatology and Gastroenterology, Cliniques St Luc, Brussels, Belgium; University of Hawaii, Honolulu, HI; Bristol-Myers Squibb Co. (BMS), Research and Development, Wallingford, CT; Bristol-Myers Squibb Co., Research and Development, Princeton, NJ.

1/26/10

Reference
TT Chang, CL Lai, S Kew Yoon, and others. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology (Abstract). January 4, 2010 (Epub ahead of print).