Entecavir for the treatment of lamivudine-refractory chronic hepatitis B patients in China

Abstract

Purpose This randomized, double-blind, placebo-controlled study was undertaken to evaluate the efficacy and safety of entecavir in Chinese patients with lamivudinerefractory chronic hepatitis B.Methods One hundred forty-five lamivudine-refractory patients with chronic hepatitis B were randomized to double-blind treatment with oral entecavir 1 mg (n = 116) or placebo (n = 29) daily for 12 weeks, followed by 36 weeks of open-label entecavir treatment. The primary efficacy endpoint was the mean change from baseline in serum hepatitis B virus (HBV) DNA by polymerase chain reaction (PCR) assay at week 12.Results At week 12, the mean change from baseline in serum HBV DNA by PCR assay was -4.30 log 10 copies/ml for patients on entecavir compared to -0.15 log 10 copies/ ml for patients on placebo (P < .0001). Among patients with baseline serum alanine aminotransferase (ALT) >1 · upper limit of normal (ULN), a higher proportion of entecavir than placebo patients (68% vs. 6%, respectively) achieved ALT normalization by week 12 (P < .0001). After 48 weeks of entecavir treatment, the mean change in HBV DNA by PCR assay was -5.08 log 10 copies/ml, and 85% of patients with baseline ALT >1 · ULN had achieved ALT normalization. The safety profile of entecavir was similar to that of placebo during the first 12 weeks of blinded dosing. Entecavir was also well tolerated during 36 weeks of open-label treatment. Conclusions Lamivudine-refractory chronic hepatitis B patients treated with entecavir demonstrated marked HBV DNA reduction and normalization of ALT in most cases. Entecavir treatment for 48 weeks was well tolerated.

Entecavir plus adefovir versus adefovir plus lamivudine in hepatitis B virus e antigen‐positive, lamivudine‐resistant chronic hepatitis B

“…The week 48 virologic results with ETV monotherapy were consistent with those described previously for ETV in LAMrefractory or LAM-resistant populations; 30,[39][40][41][42] efficacy data from the second year are of limited value, as they reflect a mixed treatment strategy, with 33 patients adding TDF after week 48.…”

“…In all three arms, serologic response rates were low (HBeAg seroconversion rates < 10%), a finding which has been reported previously in LAM-experienced patients receiving rescue therapy, 30,[40][41][42] and which may be due to extensive prior treatment selecting for HBeAg(+) patients with an inherent barrier to seroconversion. Furthermore, over 80% of the patients had HBV genotype C infection, which has been associated with a lower probability of achieving a serologic response.…”

Safety and efficacy of entecavir for the treatment of chronic hepatitis B

“…Phase II and III studies in the more difficult-to-treat lamivudine-refractory population were completed in multinational12,18 and Asian cohorts 19,20. Week 48 HBV DNA suppression was not as robust as seen in naïve patients, with mean decreases of about 5 log copies/mL.…”

Early hepatitis B virus DNA reduction in hepatitis B e antigen–positive patients with chronic hepatitis B

“…11 Therapy with ETV resulted in superior histological, biochemical, and virological efficacy after 1 year of treatment compared with lamivudine in HBeAg-positive and HBeAg-negative patients with CHB. [12][13][14][15][16] Follow-up of patients treated in clinical trials beyond 48 weeks demonstrated durable viral suppression. [17][18][19][20] Viral kinetic studies of nucleoside analogs have shown a biphasic decay in HBV DNA.…”