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Background & Aims: Entecavir demonstrated superior benefit to lamivudine at 48 weeks in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). We evaluated continued entecavir and lamivudine treatment through 96 weeks. Methods: 709 HBeAg-positive CHB patients were randomized to entecavir 0.5 mg (n = 354) or lamivudine 100 mg (n = 355) once daily. At week 52, protocol-defined virologic responders could continue blinded treatment for up to 96 weeks. Patients continuing in year 2 (entecavir, n = 243; lamivudine, n = 164) were assessed for serum hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT) normalization, HBeAg seroconversion, and safety. Cumulative confirmed proportions of all treated patients who achieved these responses were also analyzed. Results: Among patients treated in year 2, 74% of entecavir-treated versus 37% of lamivudine-treated patients achieved HBV DNA <300 copies/mL by polymerase chain reaction (PCR), and 79% of entecavir-treated versus 68% of lamivudine-treated patients normalized ALT levels. Similar proportions of entecavir-treated and lamivudine-treated patients achieved HBeAg seroconversion (11% vs 12%, respectively). Higher proportions of entecavir-treated than lamivudine-treated patients achieved cumulative confirmed HBV DNA <300 copies/mL by PCR (80% vs 39%; P < .0001) and ALT normalization (87% vs 79%; P = .0056) through 96 weeks. Cumulative confirmed HBeAg seroconversion occurred in 31% of entecavir-treated versus 25% of lamivudine-treated patients (P = NS). Through 96 weeks, no patient experienced virologic breakthrough due to entecavir resistance. The safety profile was comparable in both groups. Conclusions: Entecavir treatment through 96 weeks results in continued benefit for patients with HBeAg-positive CHB. Abbreviations used in this paper: bDNA, branched DNA, CHB, chronic hepatitis B, PCR, polymerase chain reaction, ULN, upper limit of normal ⁎ Division of Hepatology and Complex GI, California Pacific Medical Center, San Francisco, California ‡ Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan § Department of Internal Medicine, National Cheng Kung University Medical College, Tainan, Taiwan ∥ Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Hospital Rotterdam, Rotterdam, The Netherlands ¶ Sección Hepatología, Hospital Italiano, Buenos Aires, Argentina # Section of Gastroenterology, University of Santo Tomas, Manila, Philippines ⁎⁎ Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea ‡‡ Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan §§ Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan ∥∥ Bristol-Myers Squibb, Research and Development, Plainsboro, New Jersey ¶¶ Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut
The study was sponsored by Bristol-Myers Squibb. The sponsor designed the study in collaboration with expert hepatologists. The sponsor also collected the data, monitored study conduct, performed the statistical analyses, and coordinated writing of the manuscript with all authors. The study was conducted in accordance with the ethics principles of the Declaration of Helsinki and in line with Good Clinical Practice guidelines and applicable local regulatory requirements. Written informed consent was obtained from all participants, and financial disclosures were documented and submitted to the U.S. Food and Drug Administration. Statistical analyses were performed in accordance with the Good Clinical Practice guidelines, and the product was subsequently approved by the U.S. Food and Drug Administration. R.G.G. had full access to all the data and accepts full responsibility for the veracity of the data and analysis. The authors declare the following conflicts of interest: R.G.G. received a research grant from, and is an advisor to, Bristol-Myers Squibb, A.S.L. received a research grant from Bristol-Myers Squibb, A.S.L., A.G., and K.-H.H. are advisors for Bristol-Myers Squibb, and M.H., J.Y., R.C., H.B.-S. are employees of Bristol-Myers Squibb. T.-T.C., R.A.D., J.S., Y.-C.C., and S.-D.L. have no financial arrangements to disclose. PII: S0016-5085(07)01482-5 doi:10.1053/j.gastro.2007.08.025 © 2007 AGA Institute. Published by Elsevier Inc. All rights reserved.
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ABSTRACT
Entecavir Therapy for up to 96 Weeks in Patients With HBeAg-Positive Chronic Hepatitis B