Viral Hepatitis

Efficacy and safety of entecavir versus adefovir in chronic hepatitis B patients with hepatic decompensation: A randomized, open-label study

Liaw, Yun-Fan¹; Raptopoulou-Gigi, Maria²; Cheinquer, Hugo³; Sarin, Shiv Kumar⁴; Tanwandee, Tawesak⁵; Leung, Nancy⁶; Peng, Cheng-Yuan⁷; Myers, Robert P.⁸; Brown, Robert S. Jr⁹; Jeffers, Lennox¹⁰; Tsai, Naoky¹¹; Bialkowska, Jolanta¹²; Tang, Shijie¹³; Beebe, Suzanne¹³; Cooney, Elizabeth¹³

Author Information

¹Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan

²Second Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

³Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil

⁴Department of Gastroenterology, G. B. Pant Hospital, New Delhi, India

⁵Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

⁶Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China

⁷China Medical University Hospital, Taichung, Taiwan

⁸Liver Unit, University of Calgary, Calgary, Alberta, Canada

⁹Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, NY

¹⁰Miami Veterans Affairs Medical Center, Miami, FL

¹¹John A. Burns School of Medicine, University of Hawaii, Honolulu, HI

¹²Department of Infectious Diseases, Medical University, Lodz, Poland

¹³Research and Development, Bristol-Myers Squibb Co., Wallingford, CT

Liver Research Unit, Chang Gung University and Memorial Hospital, 199, Tung Hwa North Road, Taipei 105, Taiwan E-mail:[email protected]

Potential conflict of interest: This study was sponsored by Bristol-Myers Squibb Pharmaceutical Research Institute. Professor Liaw received grant/research support from Bristol-Myers Squibb, Novartis, Roche, and Gilead Sciences and serves as a consultant to Bristol-Myers Squibb, Novartis, and Roche. Professor Cheinquer received research grants from Bristol-Myers Squibb and Roche and serves on advisory boards of Bristol-Myers Squibb and Roche. Dr. Tsai serves on the speakers bureaus of Bristol-Myers Squibb, Gilead Sciences, and Roche/Genentech; serves as a consultant to Bristol-Myers Squibb and Gilead Sciences; has received honoraria from Bristol-Myers Squibb, Gilead Sciences, and Roche/Genentech; and has received research grants from Bristol-Myers Squibb, Gilead Sciences, Roche/Genetech, and Novartis. Dr. Peng serves on the advisory boards of Bristol-Myers Squibb, Novartis, and Roche. S. Tang, S. Beebe, and E. Cooney are employees of Bristol-Myers Squibb. The following individuals have nothing to disclose: Professor Raptopoulou-Gigi, Dr. Sarin, Dr. Tanwandee, Professor Leung, Dr. Myers, Dr. Brown, and Dr. Jeffers.

fax: 886–3–3282824

Hepatology 54(1):p 91-100, July 2011. | DOI: 10.1002/hep.24361

Abstract

A randomized, open-label comparative study of entecavir versus adefovir therapy was performed in subjects with chronic hepatitis B who had hepatic decompensation (Child-Turcotte-Pugh score ≥7). Adult subjects were randomized and treated (n = 191) with entecavir 1.0 mg or adefovir 10 mg daily for up to 96 weeks from the date of last subject randomization. Subjects were positive or negative for hepatitis B e antigen and experienced or naive for treatment with nucleos(t)ide analogues. The primary efficacy endpoint was the mean reduction in serum hepatitis B virus (HBV) DNA, as determined by polymerase chain reaction, at week 24, adjusted for baseline HBV DNA and lamivudine resistance status by linear regression analysis. Entecavir demonstrated superiority to adefovir for this endpoint (treatment difference 1.74 log₁₀ copies/mL [95% confidence interval −2.30, −1.18]; P < 0.0001). The entecavir group showed a greater change from baseline in HBV DNA at all time points through week 48 and a higher proportion of subjects who achieved HBV DNA < 300 copies/mL at weeks 24 (entecavir 49%; adefovir 16%; P < 0.0001) and 48 (entecavir 57%; adefovir 20%; P < 0.0001). Approximately two-thirds of subjects in both groups showed improvement/stabilization in Child-Turcotte-Pugh status. Model for End-Stage Liver Disease score change at week 48 was −2.6 for entecavir and −1.7 for adefovir. Adverse event rates were comparable between groups. Cumulative hepatocellular carcinoma rates were 12% for entecavir and 20% for adefovir. Cumulative death rates were 23% for entecavir and 33% for adefovir. Week 24 mortality rates were 12% for both groups. Conclusion: Entecavir demonstrated superior virologic efficacy to adefovir in a population of patients with chronic hepatitis B who had hepatic decompensation. Biochemical and clinical benefits were also demonstrated. Entecavir was well tolerated, and early mortality rates were consistent with rates observed in similar populations treated with lamivudine. (HEPATOLOGY 2011;)