NEJM 2005;354(10):1001-1010
A Comparison of Entecavir and Lamivudine for HBeAg-Positive Chronic
Hepatitis B
Ting-Tsung Chang, M.D., Robert G. Gish, M.D., Robert de Man, M.D., Adrian Gadano, M.D., José Sollano, M.D., You-Chen Chao, M.D., Anna S. Lok, M.D., Kwang-Hyub Han, M.D., Zachary Goodman, M.D., Ph.D., Jin Zhu,
Ph.D., Anne Cross, Ph.D., Deborah DeHertogh, M.D., Richard Wilber, M.D., Richard Colonno, Ph.D., David Apelian, M.D., Ph.D., for the BEHoLD AI463022 Study Group
ABSTRACT
Background Entecavir is a potent and selective guanosine analoguewith significant activity against hepatitis B virus (HBV).
Methods In this phase 3, double-blind trial, we randomly assigned715 patients with hepatitis B e antigen (HBeAg)–positivechronic hepatitis B who had not previously received a nucleoside analogue to receive either 0.5 mg of entecavir or 100 mg oflamivudine once daily for a
minimum of 52 weeks. The primaryefficacy end point was histologic improvement (a decrease byat least two points in the Knodell necroinflammatory score,without worsening of fibrosis) at week 48. Secondary end pointsincluded a reduction in the serum HBV DNA level, HBeAg loss and seroconversion, and normalization of the alanine aminotransferaselevel.
Results Histologic improvement after 48 weeks occurred in 226of 314 patients in the entecavir group (72 percent) and 195of 314 patients in the lamivudine group (62 percent, P=0.009).More patients in the entecavir group than in the lamivudinegroup had undetectable serum HBV DNA levels according to a polymerase-chain-reactionassay (67 percent vs. 36 percent, P<0.001) and normalizationof alanine aminotransferase levels (68 percent vs. 60 percent,P=0.02). The mean reduction in serum HBV DNA from baseline toweek 48 was greater with entecavir than with lamivudine (6.9vs. 5.4 log [on a base-10 scale] copies per milliliter, P<0.001).HBeAg seroconversion occurred in 21 percent of entecavir-treatedpatients and 18 percent of those treated with lamivudine (P=0.33).No viral resistance to entecavir was detected. Safety was similarin the two groups.
Conclusions Among patients with HBeAg-positive chronic hepatitisB, the rates of histologic, virologic, and biochemical improvementare significantly higher with entecavir than with lamivudine.The safety profile of the two agents is similar, and there isno evidence of viral resistance to entecavir. ClinicalTrials.govnumber, NCT00035633
Source Information
From the National Cheng Kung University Medical College, Tainan, Taiwan (T.-T.C.); California Pacific Medical Center, San Francisco (R.G.G.); University Hospital Rotterdam, Rotterdam, the Netherlands (R.M.); Hospital Italiano, Buenos Aires (A.G.); the University of Santo Tomas, Manila, the Philippines (J.S.); Tri-Service General Hospital, Taipei, Taiwan (Y.-C.C.); the University of Michigan, Ann Arbor (A.S.L.); Severance Hospital, Yonsei University College of Medicine, Seoul, Korea (K.-H.H.); Armed Forces Institute of Pathology, Washington, D.C. (Z.G.); Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Conn. (J.Z., A.C., R.W., R.C.); the University of Connecticut, Farmington (D.D.); and GlobeImmune, Louisville, Colo. (D.A.).
