Early hepatitis B virus DNA reduction in hepatitis B e antigen-positive patients with chronic hepatitis B: A randomized international study of entecavir versus adefovir

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http://www3.interscience.wiley.com/journal/121422510/abstract

Hepatology

Published Online: 26 Sep 2008

Viral Hepatitis

Early hepatitis B virus DNA reduction in hepatitis B e antigen-positive patients

with chronic hepatitis B: A randomized international study of entecavir versus

adefovir§

Leung 1 *¶, Cheng-Yuan Peng 2, Hie-Won Hann 3, Sollano 4, Judy

Lao-Tan 5, Chao-Wei Hsu 6, tius Lesmana 7, Man-Fung Yuen 8, Lennox Jeffers

9, Sherman 10, Albert Min 11, Mencarini 12, Ulysses Diva 12,

Anne Cross 12, Wilber 12, -Talavera 12

1Alice Ho Miu Ling Nethersole Hospital, Taipo, Hong Kong SAR, China

2China Medical University Hospital, Taichung, Taiwan

3 Jefferson University Hospital, Philadelphia, PA

4University of Santo Tomas, Manila, the Philippines

5Cebu Doctors University Hospital, Cebu City, Philippines

6Chang Gung Memorial Hospital, Chang Gung University College of Medicine,

Taipei, Taiwan

7University of Indonesia, Jakarta, Indonesia

8Queen Hospital, Pok Fu Lam, Hong Kong, SAR, China

9University of Miami Center for Liver Diseases, Miami, FL

10Toronto General Hospital, Toronto, Ontario, Canada

11Beth Israel Medical Center, New York, NY

12Bristol Myers-Squibb, Research & Development, Wallingford, CT

email: Leung (leungwyn@...

*Correspondence to Leung, Department of Medicine, Alice Ho Miu Ling

Nethersole Hospital, 11 Chuen On Road, Taipo, NT, Hong Kong, SAR (China)

Presented in part at the National Institute of Health Liver Meeting 2006, April

6-8, 2006; the 12th International Symposium on Viral Hepatitis and Liver

Disease, July 4, 2006; the 56th Annual Meeting of the American Association for

the Study of Liver Diseases, October 30 2006; the 42nd Annual Meeting of the

European Association for the Study of the Liver, April 11-15, 2007.

Clinical trial registration number: NCT00096785.

§Potential conflict of interest: Nothing to report.

¶fax: (85) 2-2689-3623

Abstract

This study was undertaken to compare the early antiviral activity and viral

kinetic profiles of entecavir (ETV) versus adefovir (ADV) in hepatitis B e

antigen positive nucleoside-naïve adults with chronic hepatitis B (CHB).

Sixty-nine nucleoside-naïve CHB patients with baseline HBV DNA of 108 copies/mL

or more were randomized 1:1 to open-label treatment with entecavir 0.5 mg/day or

adefovir 10 mg/day for a minimum of 52 weeks. The primary efficacy analysis

compared mean reduction in HBV DNA at week 12 adjusted for baseline levels using

linear regression. Entecavir was superior to adefovir for mean change from

baseline in HBV DNA at week 12 (-6.23 log10 copies/mL versus -4.42 log10

copies/mL, respectively; mean difference -1.58 log10 copies/mL; P < 0.0001).

Both drugs demonstrated biphasic viral kinetics, with a first phase of rapid

decline lasting 10 days. A significant difference favoring ETV was reached at

day 10 (day 10 ETV-ADV difference estimate: -0.66 log10 copies/mL; 95% CI

[-0.30, -0.01]). Early virological response was found to be predictive of

subsequent virological response, with those having lower HBV DNA levels at day

10 being more likely to achieve HBV DNA of less than 300 copies/mL at week 48.

In addition, there was considerably less variability in the extent of HBV DNA

reductions in patients treated with entecavir versus adefovir. Both the mean

decrease in serum HBV DNA and the proportion of patients achieving HBV DNA less

than 300 copies/mL were greater in entecavir-treated than adefovir-treated

patients at weeks 2, 4, 8, 12, 24, and 48. At week 48, one (3%) ETV-treated

versus 15 (47%) ADV-treated patients had HBV DNA of 105 copies/mL or more. Both

antivirals were well tolerated. Conclusion: Entecavir therapy resulted in

earlier and superior reduction in HBV DNA compared with adefovir in

nucleoside-naïve HBeAg-positive patients with CHB. (HEPATOLOGY 2008.)

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Received: 30 May 2008; Accepted: 4 August 2008

Digital Object Identifier (DOI)

10.1002/hep.22658