Entecavir Therapy for up to 96 Weeks in Patients With HBeAg-Positive Chronic Hepatitis B
Authors
Robert G. Gish ; Anna S. Lok ; Helena Brett–Smit ; Richard Colonno ; Joanna Yang ; Melissa Harris ; Shou–Dong Lee ; You–Chen Chao ; Kwang–Hyub Han ; José Sollano ; Adrian Gadano ; Robert A. de Man ; Ting–Tsung Chang
Alanine Transaminase/blood ; Antiviral Agents/adverse effects ; Antiviral Agents/therapeutic use* ; DNA, Viral/blood ; Dose-Response Relationship, Drug ; Double-Blind Method ; Guanine/adverse effects ; Guanine/analogs & derivatives* ; Guanine/therapeutic use ; Hepatitis B e Antigens/blood* ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B, Chronic/immunology* ; Humans ; Lamivudine/adverse effects ; Lamivudine/therapeutic use
Abstract
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.