Effect of Telbivudine Versus Other Nucleos(t)ide Analogs on HBeAg Seroconversion and Other Outcomes in Patients with Chronic Hepatitis B: A Network Meta-Analysis

Adv Ther. 2016 Apr;33(4):519-31. doi: 10.1007/s12325-016-0305-x. Epub 2016 Feb 26.

Abstract

Introduction: A comprehensive and up-to-date network meta-analysis (NMA) helps to determine the comparative efficacies of nucleos(t)ide analogs (NAs) in patients with chronic hepatitis B (CHB). The aim of this NMA was to assess the efficacy of telbivudine versus adefovir, entecavir, lamivudine, and tenofovir in nucleos(t)ide-naïve hepatitis B e antigen (HBeAg)-positive patients with CHB.

Methods: A systematic review was conducted to search Medline, Medline-In Process, EMBASE, and the Cochrane Central Register of Controlled Trials databases for publications of randomized controlled trials (RCTs). NMA was performed to compare the efficacy outcomes of telbivudine versus other approved NAs at 1- and 2-year time points.

Results: A total of 75 RCTs were included in the systematic review. At the 1-year time point, telbivudine was associated with significantly higher rates of: (1) HBeAg seroconversion than adefovir [odds ratio (OR) 1.99 (95% credible interval (CrI): 1.05, 3.45)], entecavir [OR 2.00 (95% CrI: 1.44, 2.82)] and lamivudine [OR 1.49 (95% CrI: 1.10, 2.03)]; (2) HBeAg loss than entecavir [OR 1.85 (95% CrI: 1.28, 2.76)] and lamivudine [OR 1.62 (95% CrI: 1.20, 2.24)]; (3) alanine aminotransferase (ALT) normalization than lamivudine [OR 1.50 (95% CrI: 1.05, 2.21)]; and (4) hepatitis B virus (HBV) DNA suppression than adefovir [OR 2.77 (95% CrI: 1.28, 5.45)] and lamivudine [OR 2.97 (95% CrI: 1.99, 4.53)]. At the 2-year time point, the relative efficacy outcomes were not statistically significant.

Conclusion: At 1 year, telbivudine was superior to adefovir, entecavir and lamivudine in HBeAg seroconversion, and to entecavir and lamivudine in HBeAg loss. Telbivudine was also superior to lamivudine in ALT normalization and to adefovir and lamivudine in suppressing HBV DNA levels.

Funding: Novartis Pharma AG.

Keywords: Alanine aminotransferase; Chronic hepatitis B; Cirrhosis; Hepatitis B e antigen seroconversion; Infectious diseases; Meta-analysis; Nucleos(t)ide analogs.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antiviral Agents / classification
  • Antiviral Agents / pharmacology
  • Comparative Effectiveness Research
  • Hepatitis B e Antigens* / blood
  • Hepatitis B e Antigens* / immunology
  • Hepatitis B, Chronic* / drug therapy
  • Hepatitis B, Chronic* / immunology
  • Humans
  • Nucleic Acid Synthesis Inhibitors* / classification
  • Nucleic Acid Synthesis Inhibitors* / pharmacology
  • Randomized Controlled Trials as Topic
  • Seroconversion / drug effects
  • Telbivudine
  • Thymidine / analogs & derivatives*
  • Thymidine / pharmacology
  • Time
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Hepatitis B e Antigens
  • Nucleic Acid Synthesis Inhibitors
  • Telbivudine
  • Thymidine