Efficacy and Safety of Telbivudine Compared to Entecavir Among HBeAg+ Chronic Hepatitis B Patients: a Meta-Analysis Study

Abstract

BackgroundHepatitis B virus (HBV) infection is a serious global health problem that is associated with huge social and economic costs. Early antiviral drugs, such as interferon-α2b, peginterferon-α2a, lamivudine, and adefovir, all have their limitations (such as low responses or safety concerns) in clinical application. Telbivudine and entecavir are two of the latest nucleotide drugs and both have been shown to have potent viral suppression. However, in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB), inconsistent results have been generated for efficacy between telbivudine and entecavir. Therefore, evidence-based medical data are required to compare the efficacies, in terms of virological and biochemical responses, and safety between telbivudine and entecavir.ObjectivesWe aimed to compare the early antiviral efficacy and safety of telbivudine and entecavir in the treatment of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB).Patients and MethodsA search for relevant randomized controlled trials (RCTs) on HBeAg-positive CHB patients treated with telbivudine and entecavir for 24 or 52 weeks, published before December 2011, was performed. Primary efficacy endpoint was the cumulative rate of undetectable HBV DNA, and secondary efficacy endpoints included rates of alanine aminotransferase (ALT) normalization, HBeAg disappearance, HBeAg seroconversion and adverse events. Meta-analysis was performed using the Review Manager v5.1.4 software package. We assessed the pooled risk ratios (RRs) and 95% confidence intervals (CIs) using the fixed-or random-effects model.ResultsSix randomized controlled trials (RCTs) involving 555 patients were included. Telbivudine was associated with significantly higher rates of HBeAg disappearance (RR = 1.46, 95% CI: 1.11 - 1.91) and HBeAg seroconversion (RR = 1.76, 95%CI: 1.25-2.48) than entecavir, but had higher adverse events (RR = 2.11, 95%CI: 1.23 - 3.60), compared with entecavir. There was no difference between telbivudine and entecavir in the rate of cumulative undetectable HBV DNA (RR = 0.99, 95% CI: 0.90 - 1.10) and ALT normalization (RR = 0.93, 95% CI: 0.85 - 1.00).ConclusionsTelbivudine is associated with significantly higher rates of HBeAg disappearance and HBeAg seroconversion than entecavir, whereas entecavir is superior to telbivudine in safety. Both drugs have similar efficacy on rates of cumulative undetectable HBV DNA and ALT normalization.

Approved Antiviral Drugs over the Past 50 Years

“…For treatment of HBeAg ϩ mothers during late pregnancy, telbivudine was well tolerated, with no severe side effects in telbivudine-treated mothers or their infants (112). Although entecavir is superior to telbivudine in safety, both telbivudine and entecavir offer similar drug efficacies in terms of the cumulative rates of undetectable HBV DNA and alanine aminotransferase levels (113). For first-line therapy of HBV infections, the use of entecavir is strongly recommended, especially in children aged 2 to 12 years (114).…”

Efficacy and resistance to telbivudine treatment in chronic hepatitis B patients with favorable predictors: a multicenter study in Taiwan

“…A systemic review also confirmed these findings [31]. Compared with ETV, which bears a high genetic barrier to drug resistance, several meta-analyses indicated that shortterm LdT treatment had a more favorable serologic response than ETV, but a higher rate of genotypic resistance [32][33][34]. Nevertheless, several advantages of LdT such as its safety for pregnant females [35] and improvement of renal function in patients with baseline mild renal dysfunction [36] should not be overlooked.…”

Telbivudine therapy for chronic hepatitis B: A journey to identify super‐responders and to optimize treatment using the roadmap model

“…Telbivudine, a potent antiviral, is an orally administered synthetic thymidine nucleoside analog with specific activity against HBV . The general efficacy of telbivudine (ability to reduce HBV DNA and ALT levels and stimulate HBeAg seroconversion) has been discussed extensively in literature reviews and meta‐analyses . A more recent network meta‐analysis demonstrated the superiority of telbivudine over adefovir, entecavir, and lamivudine in HBeAg seroconversion or HBeAg loss .…”

“…18,27 The general efficacy of telbivudine (ability to reduce HBV DNA and ALT levels and stimulate HBeAg seroconversion) has been discussed extensively in literature reviews and meta-analyses. [28][29][30] A more recent network meta-analysis demonstrated the superiority of telbivudine over adefovir, entecavir, and lamivudine in HBeAg seroconversion or HBeAg loss. 31 Although the short-term efficacy of telbivudine with regard to the rate of undetectable HBV DNA level appears to be comparable with entecavir, the results showed improved suppression of HBV DNA with long-term telbivudine treatment in comparison with adefovir and lamivudine.…”