Long-term efficacy and safety of adefovir dipivoxil for the ... : Hepatology (original) (raw)

Viral Hepatitis

Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen–positive chronic hepatitis B

Marcellin, Patrick1*; Chang, Ting-Tsung2; Lim, Seng G. Lee3; Sievert, William4; Tong, Myron5; Arterburn, Sarah6; Borroto-Esoda, Katyna6; Frederick, David6; Rousseau, Franck6

1_Hopital Beaujon, Paris, France_

2_National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China_

3_National University Health System, Singapore_

4_Monash University and Monash Medical Center, Melbourne, Australia_

5_Phleger Liver Institute, Division of Gastroenterology, David Geffen School of Medicine at UCLA, Los Angeles, CA_

6_Gilead Sciences, Inc, Foster City, CA_

* Address reprint requests to: Service d'Hépatologie, Hôpital Beaujon, AP-HP, Université Paris VII, 92110 Clichy–France

Email:[email protected]

Received 31 August 2007; Accepted 2 May 2008

Published online in Wiley InterScience (www.interscience.wiley.com).

Supported by Gilead Sciences.

Potential conflict of interest: Drs. Arterburn, Borroto-Esoda, Frederick, and Rousseau own stock in Gilead Sciences. Dr. Lim advises Novartis, Bristol-Myers Squibb, and Schering-Plough. He is on the speakers' bureau of GlaxoSmithKline. Dr. Marcellin advises, is on the speakers' bureau of Roche, Schering-Plough, Gilead, Bristol-Myers Squibb, GlaxoSmithKline, and Idenix-Novartis. He is also a consultant and advises Vertex, Valeant, Cytheris, Intermune, Wyeth, and Tibotec. Dr. Sievert is on the Speakers' bureau of Gilead Sciences.

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Abstract

Treatment of 171 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with adefovir dipivoxil (ADV) 10 mg over 48 weeks resulted in significant histological, virological, serological, and biochemical improvement compared with placebo. The long-term efficacy and safety of ADV in a subset of these patients was investigated for up to 5 years. Sixty-five patients given ADV 10 mg in year 1 elected to continue in a long-term safety and efficacy study (LTSES). At enrollment, the 65 LTSES patients were a median 34 years old, 83% male, 74% Asian, 23% Caucasian, median baseline serum hepatitis B virus (HBV) DNA 8.45 log10 copies/mL, and median baseline alanine aminotransferase (ALT) 2.0 × upper limit of normal. At 5 years on study, the median changes from baseline in serum HBV DNA and ALT for the 41 patients still on ADV were 4.05 log10 copies/mL and −50 U/L, respectively. HBeAg loss and seroconversion were observed in 58% and 48% of patients by end of study, respectively. Fifteen patients had baseline and end of follow-up liver biopsies; improvements in necroinflammation and fibrosis were seen in 67% and 60% of these patients, respectively. Adefovir resistance mutations A181V or N236T developed in 13 LTSES patients; the first observation was at study week 195. There were no serious adverse events related to ADV. Conclusion: Treatment with ADV beyond 48 weeks was well tolerated and produced long-term virological, biochemical, serological, and histological improvement. (Hepatology 2008;48:750–758.)

Abbreviations: ADV, adefovir dipivoxil; ADV10-Y1, patients who received at least one dose of ADV 10 mg in year 1 of the study; AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CHB, chronic hepatitis B; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; LTSES, long-term safety and efficacy study; OL, open-label; ULN, upper limit of normal.