Helena Brett-Smith

Efficacy and safety of entecavir in patients with chronic hepatitis B and advanced hepatic fibrosis or cirrhosis.

OBJECTIVE: The efficacy and safety of entecavir in patients with chronic hepatitis B and advanced liver fibrosis/cirrhosis was assessed from three large, randomized, multicenter, phase III studies.PATIENTS AND METHODS:These studies enrolled patients (≥16 yr) with chronic hepatitis B, elevated alanine aminotransferase (ALT) levels, and compensated liver disease. Two trials enrolled nucleos(t)ide-naive patients randomized to at least 48 wk of treatment with entecavir 0.5 mg/day or lamivudine 100 mg/day. The third trial randomized lamivudine-refractory patients to 48 wk of entecavir 1 mg/day or lamivudine 100 mg/day. In this post hoc descriptive analysis, the efficacy and safety in patients with advanced liver fibrosis/cirrhosis (Ishak fibrosis stages 4–6) were examined for consistency with those seen in the overall study populations.RESULTS: Of the 1,633 treated patients, 245 had advanced liver fibrosis/cirrhosis (120 entecavir and 125 lamivudine). Among entecavir-treated patients with advanced liver fibrosis, improvement in Ishak fibrosis was observed in 57% of nucleos(t)ide-naive hepatitis B e antigen (HBeAg)-positive patients, 59% of nucleos(t)ide-naive HBeAg-negative patients, and 43% of lamivudine-refractory HBeAg-positive patients versus 49%, 53%, and 33% of lamivudine-treated patients with advanced liver fibrosis. The overall trends in other histologic, virologic, biochemical, and serologic outcomes in entecavir- versus lamivudine-treated patients with advanced liver fibrosis/cirrhosis were consistent with those observed in the overall study populations in each trial. The treatment was well tolerated.CONCLUSION: These data confirm that the performance of entecavir relative to that of lamivudine in patients with advanced liver fibrosis/cirrhosis was consistent with the relationship observed in the overall treated population.

Loss of HBsAg antigen during treatment with entecavir or lamivudine in nucleoside‐naïve HBeAg‐positive patients with chronic hepatitis B

Summary.  This retrospective analysis was conducted to describe the characteristics of nucleoside‐naïve hepatitis B e antigen (HBeAg)‐positive patients with chronic hepatitis B, who achieved hepatitis B surface antigen (HBsAg) loss during entecavir or lamivudine therapy. HBeAg‐positive adults with chronic hepatitis B, elevated serum alanine aminotransferase, and compensated liver disease were randomized to double‐blind treatment for up to 96 weeks with entecavir 0.5 mg/day or lamivudine 100 mg/day. HBsAg and hepatitis B virus (HBV) DNA were measured at regular intervals during and off‐treatment follow‐up. Through a maximum duration of 96 weeks on‐treatment and 24 weeks off‐treatment, HBsAg loss was confirmed in 18/354 (5.1%) patients treated with entecavir and 10/355 (2.8%) patients treated with lamivudine. Among the 28 patients with confirmed HBsAg loss, 27 (96%) achieved HBV DNA <300 copies/mL, and 27 (96%) achieved confirmed HBeAg loss. All entecavir recipients with HBsAg loss had HBV DNA <300 copies/mL. Caucasian patients, and those infected with HBV genotype A or D, were significantly more likely to lose HBsAg. This retrospective analysis of data from a randomized, global phase three trial shows that confirmed loss of HBsAg occurred in 5% of nucleoside‐naïve HBeAg‐positive patients treated with entecavir, and that HBsAg loss is associated with sustained off‐treatment suppression of HBV DNA.

Results of up to 2 years of entecavir vs lamivudine therapy in nucleoside-naïve HBeAg-positive patients with chronic hepatitis B.

Summary.  Entecavir is a potent inhibitor of hepatitis B virus (HBV) polymerase. The efficacy and safety of entecavir in nucleoside‐naïve patients with hepatitis B virus e antigen (HBeAg)‐positive chronic hepatitis B was established in a large, international, double‐dummy study (ETV‐022) where patients were randomized to entecavir 0.5 mg/day (n = 354) or lamivudine 100 mg/day (n = 355) once daily. ETV‐022 had a 52‐week blinded treatment phase, followed by an extended blinded treatment phase for up to 44 additional weeks (96 weeks total). Treatment was discontinued for patients achieving a protocol‐defined response as determined by patient management criteria that intended to test the possibility of finite therapy, which has not previously been studied for entecavir or other anti‐HBV agents in a large trial. Early results from this study have been previously presented/published separately. This paper compiles the results of up to 2 years of treatment for protocol‐defined responders, virologic responders and nonresponders. For responders who discontinued therapy (per protocol), 24‐week off‐treatment evaluation is presented to provide a more ‘complete picture’ of what clinicians can expect when treating nucleoside‐naïve HBeAg‐positive patients with chronic hepatitis B. For patients who discontinued therapy because of nonresponse (nonresponders) and subsequently entered the rollover study ETV‐901, follow‐up results, including resistance profile, are provided.

W1805 Entecavir Maintains a High Genetic Barrier to HBV Resistance Through 6 Years in NaïVE Patients

• Resistance is rare through 6 years – 1.2% cumulative probability of genotypic resistance. LVD-Refractory: • The 6 year cumulative probability of genotypic resistance is 57%. – 74/187 (40%) patients achieved HBV DNA < 300 c/mL while on treatment with ETV; of those 74 patients, only 5 (7%) subsequently developed genotypic ETV resistance. Entecavir Maintains a High Genetic Barrier to HBV Resistance Through 6 Years in Naïve Patients D.J. Tenney1, K.A. Pokorowski1, R.E. Rose1, C.J. Baldick1, B.J. Eggers1, J. Fang1, M.J. Wichroski1, U. Diva1, D. Xu1, R.B. Wilber1, H. Brett-Smith1 & U.H. Iloeje1 1Research and Development, Bristol-Myers Squibb Company, United States